Rare recurrent copy number variations in metabotropic glutamate receptor interacting genes in children with neurodevelopmental disorders

Background Neurodevelopmental disorders (NDDs), such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are examples of complex and partially overlapping phenotypes that often lack definitive corroborating genetic information. ADHD and ASD have complex genetic ass...

Full description

Saved in:
Bibliographic Details
Published inJournal of neurodevelopmental disorders Vol. 15; no. 1; pp. 14 - 11
Main Authors Glessner, Joseph T., Khan, Munir E., Chang, Xiao, Liu, Yichuan, Otieno, F. George, Lemma, Maria, Slaby, Isabella, Hain, Heather, Mentch, Frank, Li, Jin, Kao, Charlly, Sleiman, Patrick M. A., March, Michael E., Connolly, John, Hakonarson, Hakon
Format Journal Article
LanguageEnglish
Published London BioMed Central 29.04.2023
BioMed Central Ltd
BMC
Subjects
Online AccessGet full text
ISSN1866-1955
1866-1947
1866-1955
DOI10.1186/s11689-023-09483-z

Cover

Abstract Background Neurodevelopmental disorders (NDDs), such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are examples of complex and partially overlapping phenotypes that often lack definitive corroborating genetic information. ADHD and ASD have complex genetic associations implicated by rare recurrent copy number variations (CNVs). Both of these NDDs have been shown to share similar biological etiologies as well as genetic pleiotropy. Methods Platforms aimed at investigating genetic-based associations, such as high-density microarray technologies, have been groundbreaking techniques in the field of complex diseases, aimed at elucidating the underlying disease biology. Previous studies have uncovered CNVs associated with genes within shared candidate genomic networks, including glutamate receptor genes, across multiple different NDDs. To examine shared biological pathways across two of the most common NDDs, we investigated CNVs across 15,689 individuals with ADHD ( n  = 7920), ASD ( n  = 4318), or both ( n  = 3,416), as well as 19,993 controls. Cases and controls were matched by genotype array (i.e., Illumina array versions). Three case–control association studies each calculated and compared the observed vs. expected frequency of CNVs across individual genes, loci, pathways, and gene networks. Quality control measures of confidence in CNV-calling, prior to association analyses, included visual inspection of genotype and hybridization intensity. Results Here, we report results from CNV analysis in search for individual genes, loci, pathways, and gene networks. To extend our previous observations implicating a key role of the metabotropic glutamate receptor (mGluR) network in both ADHD and autism, we exhaustively queried patients with ASD and/or ADHD for CNVs associated with the 273 genomic regions of interest within the mGluR gene network (genes with one or two degrees protein–protein interaction with mGluR 1–8 genes). Among CNVs in mGluR network genes, we uncovered CNTN4 deletions enriched in NDD cases ( P  = 3.22E − 26, OR = 2.49). Additionally, we uncovered PRLHR deletions in 40 ADHD cases and 12 controls ( P  = 5.26E − 13, OR = 8.45) as well as clinically diagnostic relevant 22q11.2 duplications and 16p11.2 duplications in 23 ADHD + ASD cases and 9 controls ( P  = 4.08E − 13, OR = 15.05) and 22q11.2 duplications in 34 ADHD + ASD cases and 51 controls ( P  = 9.21E − 9, OR = 3.93); those control samples were not with previous 22qDS diagnosis in their EHR records. Conclusion Together, these results suggest that disruption in neuronal cell-adhesion pathways confers significant risk to NDDs and showcase that rare recurrent CNVs in CNTN4 , 22q11.2, and 16p11.2 are overrepresented in NDDs that constitute patients predominantly suffering from ADHD and ASD. Trial registration ClinicalTrials.gov Identifier: NCT02286817 First Posted: 10 November 14, ClinicalTrials.gov Identifier: NCT02777931 first posted: 19 May 2016, ClinicalTrials.gov Identifier: NCT03006367 first posted: 30 December 2016, ClinicalTrials.gov Identifier: NCT02895906 first posted: 12 September 2016.
AbstractList Background Neurodevelopmental disorders (NDDs), such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are examples of complex and partially overlapping phenotypes that often lack definitive corroborating genetic information. ADHD and ASD have complex genetic associations implicated by rare recurrent copy number variations (CNVs). Both of these NDDs have been shown to share similar biological etiologies as well as genetic pleiotropy. Methods Platforms aimed at investigating genetic-based associations, such as high-density microarray technologies, have been groundbreaking techniques in the field of complex diseases, aimed at elucidating the underlying disease biology. Previous studies have uncovered CNVs associated with genes within shared candidate genomic networks, including glutamate receptor genes, across multiple different NDDs. To examine shared biological pathways across two of the most common NDDs, we investigated CNVs across 15,689 individuals with ADHD (n = 7920), ASD (n = 4318), or both (n = 3,416), as well as 19,993 controls. Cases and controls were matched by genotype array (i.e., Illumina array versions). Three case-control association studies each calculated and compared the observed vs. expected frequency of CNVs across individual genes, loci, pathways, and gene networks. Quality control measures of confidence in CNV-calling, prior to association analyses, included visual inspection of genotype and hybridization intensity. Results Here, we report results from CNV analysis in search for individual genes, loci, pathways, and gene networks. To extend our previous observations implicating a key role of the metabotropic glutamate receptor (mGluR) network in both ADHD and autism, we exhaustively queried patients with ASD and/or ADHD for CNVs associated with the 273 genomic regions of interest within the mGluR gene network (genes with one or two degrees protein-protein interaction with mGluR 1-8 genes). Among CNVs in mGluR network genes, we uncovered CNTN4 deletions enriched in NDD cases (P = 3.22E - 26, OR = 2.49). Additionally, we uncovered PRLHR deletions in 40 ADHD cases and 12 controls (P = 5.26E - 13, OR = 8.45) as well as clinically diagnostic relevant 22q11.2 duplications and 16p11.2 duplications in 23 ADHD + ASD cases and 9 controls (P = 4.08E - 13, OR = 15.05) and 22q11.2 duplications in 34 ADHD + ASD cases and 51 controls (P = 9.21E - 9, OR = 3.93); those control samples were not with previous 22qDS diagnosis in their EHR records. Conclusion Together, these results suggest that disruption in neuronal cell-adhesion pathways confers significant risk to NDDs and showcase that rare recurrent CNVs in CNTN4, 22q11.2, and 16p11.2 are overrepresented in NDDs that constitute patients predominantly suffering from ADHD and ASD. Trial registration ClinicalTrials.gov Identifier: NCT02286817 First Posted: 10 November 14, ClinicalTrials.gov Identifier: NCT02777931 first posted: 19 May 2016, ClinicalTrials.gov Identifier: NCT03006367 first posted: 30 December 2016, ClinicalTrials.gov Identifier: NCT02895906 first posted: 12 September 2016. Keywords: Neurodevelopmental disorders, Copy number variation, Genetic association study, Autism, Attention-deficit/hyperactivity disorder, Metabotropic glutamate receptors
Neurodevelopmental disorders (NDDs), such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are examples of complex and partially overlapping phenotypes that often lack definitive corroborating genetic information. ADHD and ASD have complex genetic associations implicated by rare recurrent copy number variations (CNVs). Both of these NDDs have been shown to share similar biological etiologies as well as genetic pleiotropy.BACKGROUNDNeurodevelopmental disorders (NDDs), such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are examples of complex and partially overlapping phenotypes that often lack definitive corroborating genetic information. ADHD and ASD have complex genetic associations implicated by rare recurrent copy number variations (CNVs). Both of these NDDs have been shown to share similar biological etiologies as well as genetic pleiotropy.Platforms aimed at investigating genetic-based associations, such as high-density microarray technologies, have been groundbreaking techniques in the field of complex diseases, aimed at elucidating the underlying disease biology. Previous studies have uncovered CNVs associated with genes within shared candidate genomic networks, including glutamate receptor genes, across multiple different NDDs. To examine shared biological pathways across two of the most common NDDs, we investigated CNVs across 15,689 individuals with ADHD (n = 7920), ASD (n = 4318), or both (n = 3,416), as well as 19,993 controls. Cases and controls were matched by genotype array (i.e., Illumina array versions). Three case-control association studies each calculated and compared the observed vs. expected frequency of CNVs across individual genes, loci, pathways, and gene networks. Quality control measures of confidence in CNV-calling, prior to association analyses, included visual inspection of genotype and hybridization intensity.METHODSPlatforms aimed at investigating genetic-based associations, such as high-density microarray technologies, have been groundbreaking techniques in the field of complex diseases, aimed at elucidating the underlying disease biology. Previous studies have uncovered CNVs associated with genes within shared candidate genomic networks, including glutamate receptor genes, across multiple different NDDs. To examine shared biological pathways across two of the most common NDDs, we investigated CNVs across 15,689 individuals with ADHD (n = 7920), ASD (n = 4318), or both (n = 3,416), as well as 19,993 controls. Cases and controls were matched by genotype array (i.e., Illumina array versions). Three case-control association studies each calculated and compared the observed vs. expected frequency of CNVs across individual genes, loci, pathways, and gene networks. Quality control measures of confidence in CNV-calling, prior to association analyses, included visual inspection of genotype and hybridization intensity.Here, we report results from CNV analysis in search for individual genes, loci, pathways, and gene networks. To extend our previous observations implicating a key role of the metabotropic glutamate receptor (mGluR) network in both ADHD and autism, we exhaustively queried patients with ASD and/or ADHD for CNVs associated with the 273 genomic regions of interest within the mGluR gene network (genes with one or two degrees protein-protein interaction with mGluR 1-8 genes). Among CNVs in mGluR network genes, we uncovered CNTN4 deletions enriched in NDD cases (P = 3.22E - 26, OR = 2.49). Additionally, we uncovered PRLHR deletions in 40 ADHD cases and 12 controls (P = 5.26E - 13, OR = 8.45) as well as clinically diagnostic relevant 22q11.2 duplications and 16p11.2 duplications in 23 ADHD + ASD cases and 9 controls (P = 4.08E - 13, OR = 15.05) and 22q11.2 duplications in 34 ADHD + ASD cases and 51 controls (P = 9.21E - 9, OR = 3.93); those control samples were not with previous 22qDS diagnosis in their EHR records.RESULTSHere, we report results from CNV analysis in search for individual genes, loci, pathways, and gene networks. To extend our previous observations implicating a key role of the metabotropic glutamate receptor (mGluR) network in both ADHD and autism, we exhaustively queried patients with ASD and/or ADHD for CNVs associated with the 273 genomic regions of interest within the mGluR gene network (genes with one or two degrees protein-protein interaction with mGluR 1-8 genes). Among CNVs in mGluR network genes, we uncovered CNTN4 deletions enriched in NDD cases (P = 3.22E - 26, OR = 2.49). Additionally, we uncovered PRLHR deletions in 40 ADHD cases and 12 controls (P = 5.26E - 13, OR = 8.45) as well as clinically diagnostic relevant 22q11.2 duplications and 16p11.2 duplications in 23 ADHD + ASD cases and 9 controls (P = 4.08E - 13, OR = 15.05) and 22q11.2 duplications in 34 ADHD + ASD cases and 51 controls (P = 9.21E - 9, OR = 3.93); those control samples were not with previous 22qDS diagnosis in their EHR records.Together, these results suggest that disruption in neuronal cell-adhesion pathways confers significant risk to NDDs and showcase that rare recurrent CNVs in CNTN4, 22q11.2, and 16p11.2 are overrepresented in NDDs that constitute patients predominantly suffering from ADHD and ASD.CONCLUSIONTogether, these results suggest that disruption in neuronal cell-adhesion pathways confers significant risk to NDDs and showcase that rare recurrent CNVs in CNTN4, 22q11.2, and 16p11.2 are overrepresented in NDDs that constitute patients predominantly suffering from ADHD and ASD.ClinicalTrials.gov Identifier: NCT02286817 First Posted: 10 November 14, ClinicalTrials.gov Identifier: NCT02777931 first posted: 19 May 2016, ClinicalTrials.gov Identifier: NCT03006367 first posted: 30 December 2016, ClinicalTrials.gov Identifier: NCT02895906 first posted: 12 September 2016.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT02286817 First Posted: 10 November 14, ClinicalTrials.gov Identifier: NCT02777931 first posted: 19 May 2016, ClinicalTrials.gov Identifier: NCT03006367 first posted: 30 December 2016, ClinicalTrials.gov Identifier: NCT02895906 first posted: 12 September 2016.
Neurodevelopmental disorders (NDDs), such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are examples of complex and partially overlapping phenotypes that often lack definitive corroborating genetic information. ADHD and ASD have complex genetic associations implicated by rare recurrent copy number variations (CNVs). Both of these NDDs have been shown to share similar biological etiologies as well as genetic pleiotropy. Platforms aimed at investigating genetic-based associations, such as high-density microarray technologies, have been groundbreaking techniques in the field of complex diseases, aimed at elucidating the underlying disease biology. Previous studies have uncovered CNVs associated with genes within shared candidate genomic networks, including glutamate receptor genes, across multiple different NDDs. To examine shared biological pathways across two of the most common NDDs, we investigated CNVs across 15,689 individuals with ADHD (n = 7920), ASD (n = 4318), or both (n = 3,416), as well as 19,993 controls. Cases and controls were matched by genotype array (i.e., Illumina array versions). Three case-control association studies each calculated and compared the observed vs. expected frequency of CNVs across individual genes, loci, pathways, and gene networks. Quality control measures of confidence in CNV-calling, prior to association analyses, included visual inspection of genotype and hybridization intensity. Here, we report results from CNV analysis in search for individual genes, loci, pathways, and gene networks. To extend our previous observations implicating a key role of the metabotropic glutamate receptor (mGluR) network in both ADHD and autism, we exhaustively queried patients with ASD and/or ADHD for CNVs associated with the 273 genomic regions of interest within the mGluR gene network (genes with one or two degrees protein-protein interaction with mGluR 1-8 genes). Among CNVs in mGluR network genes, we uncovered CNTN4 deletions enriched in NDD cases (P = 3.22E - 26, OR = 2.49). Additionally, we uncovered PRLHR deletions in 40 ADHD cases and 12 controls (P = 5.26E - 13, OR = 8.45) as well as clinically diagnostic relevant 22q11.2 duplications and 16p11.2 duplications in 23 ADHD + ASD cases and 9 controls (P = 4.08E - 13, OR = 15.05) and 22q11.2 duplications in 34 ADHD + ASD cases and 51 controls (P = 9.21E - 9, OR = 3.93); those control samples were not with previous 22qDS diagnosis in their EHR records. Together, these results suggest that disruption in neuronal cell-adhesion pathways confers significant risk to NDDs and showcase that rare recurrent CNVs in CNTN4, 22q11.2, and 16p11.2 are overrepresented in NDDs that constitute patients predominantly suffering from ADHD and ASD. ClinicalTrials.gov Identifier: NCT02286817 First Posted: 10 November 14, ClinicalTrials.gov Identifier: NCT02777931 first posted: 19 May 2016, ClinicalTrials.gov Identifier: NCT03006367 first posted: 30 December 2016, ClinicalTrials.gov Identifier: NCT02895906 first posted: 12 September 2016.
BackgroundNeurodevelopmental disorders (NDDs), such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are examples of complex and partially overlapping phenotypes that often lack definitive corroborating genetic information. ADHD and ASD have complex genetic associations implicated by rare recurrent copy number variations (CNVs). Both of these NDDs have been shown to share similar biological etiologies as well as genetic pleiotropy.MethodsPlatforms aimed at investigating genetic-based associations, such as high-density microarray technologies, have been groundbreaking techniques in the field of complex diseases, aimed at elucidating the underlying disease biology. Previous studies have uncovered CNVs associated with genes within shared candidate genomic networks, including glutamate receptor genes, across multiple different NDDs. To examine shared biological pathways across two of the most common NDDs, we investigated CNVs across 15,689 individuals with ADHD (n = 7920), ASD (n = 4318), or both (n = 3,416), as well as 19,993 controls. Cases and controls were matched by genotype array (i.e., Illumina array versions). Three case–control association studies each calculated and compared the observed vs. expected frequency of CNVs across individual genes, loci, pathways, and gene networks. Quality control measures of confidence in CNV-calling, prior to association analyses, included visual inspection of genotype and hybridization intensity.ResultsHere, we report results from CNV analysis in search for individual genes, loci, pathways, and gene networks. To extend our previous observations implicating a key role of the metabotropic glutamate receptor (mGluR) network in both ADHD and autism, we exhaustively queried patients with ASD and/or ADHD for CNVs associated with the 273 genomic regions of interest within the mGluR gene network (genes with one or two degrees protein–protein interaction with mGluR 1–8 genes). Among CNVs in mGluR network genes, we uncovered CNTN4 deletions enriched in NDD cases (P = 3.22E − 26, OR = 2.49). Additionally, we uncovered PRLHR deletions in 40 ADHD cases and 12 controls (P = 5.26E − 13, OR = 8.45) as well as clinically diagnostic relevant 22q11.2 duplications and 16p11.2 duplications in 23 ADHD + ASD cases and 9 controls (P = 4.08E − 13, OR = 15.05) and 22q11.2 duplications in 34 ADHD + ASD cases and 51 controls (P = 9.21E − 9, OR = 3.93); those control samples were not with previous 22qDS diagnosis in their EHR records.ConclusionTogether, these results suggest that disruption in neuronal cell-adhesion pathways confers significant risk to NDDs and showcase that rare recurrent CNVs in CNTN4, 22q11.2, and 16p11.2 are overrepresented in NDDs that constitute patients predominantly suffering from ADHD and ASD.Trial registrationClinicalTrials.gov Identifier: NCT02286817 First Posted: 10 November 14, ClinicalTrials.gov Identifier: NCT02777931 first posted: 19 May 2016, ClinicalTrials.gov Identifier: NCT03006367 first posted: 30 December 2016, ClinicalTrials.gov Identifier: NCT02895906 first posted: 12 September 2016.
Abstract Background Neurodevelopmental disorders (NDDs), such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are examples of complex and partially overlapping phenotypes that often lack definitive corroborating genetic information. ADHD and ASD have complex genetic associations implicated by rare recurrent copy number variations (CNVs). Both of these NDDs have been shown to share similar biological etiologies as well as genetic pleiotropy. Methods Platforms aimed at investigating genetic-based associations, such as high-density microarray technologies, have been groundbreaking techniques in the field of complex diseases, aimed at elucidating the underlying disease biology. Previous studies have uncovered CNVs associated with genes within shared candidate genomic networks, including glutamate receptor genes, across multiple different NDDs. To examine shared biological pathways across two of the most common NDDs, we investigated CNVs across 15,689 individuals with ADHD (n = 7920), ASD (n = 4318), or both (n = 3,416), as well as 19,993 controls. Cases and controls were matched by genotype array (i.e., Illumina array versions). Three case–control association studies each calculated and compared the observed vs. expected frequency of CNVs across individual genes, loci, pathways, and gene networks. Quality control measures of confidence in CNV-calling, prior to association analyses, included visual inspection of genotype and hybridization intensity. Results Here, we report results from CNV analysis in search for individual genes, loci, pathways, and gene networks. To extend our previous observations implicating a key role of the metabotropic glutamate receptor (mGluR) network in both ADHD and autism, we exhaustively queried patients with ASD and/or ADHD for CNVs associated with the 273 genomic regions of interest within the mGluR gene network (genes with one or two degrees protein–protein interaction with mGluR 1–8 genes). Among CNVs in mGluR network genes, we uncovered CNTN4 deletions enriched in NDD cases (P = 3.22E − 26, OR = 2.49). Additionally, we uncovered PRLHR deletions in 40 ADHD cases and 12 controls (P = 5.26E − 13, OR = 8.45) as well as clinically diagnostic relevant 22q11.2 duplications and 16p11.2 duplications in 23 ADHD + ASD cases and 9 controls (P = 4.08E − 13, OR = 15.05) and 22q11.2 duplications in 34 ADHD + ASD cases and 51 controls (P = 9.21E − 9, OR = 3.93); those control samples were not with previous 22qDS diagnosis in their EHR records. Conclusion Together, these results suggest that disruption in neuronal cell-adhesion pathways confers significant risk to NDDs and showcase that rare recurrent CNVs in CNTN4, 22q11.2, and 16p11.2 are overrepresented in NDDs that constitute patients predominantly suffering from ADHD and ASD. Trial registration ClinicalTrials.gov Identifier: NCT02286817 First Posted: 10 November 14, ClinicalTrials.gov Identifier: NCT02777931 first posted: 19 May 2016, ClinicalTrials.gov Identifier: NCT03006367 first posted: 30 December 2016, ClinicalTrials.gov Identifier: NCT02895906 first posted: 12 September 2016.
Neurodevelopmental disorders (NDDs), such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are examples of complex and partially overlapping phenotypes that often lack definitive corroborating genetic information. ADHD and ASD have complex genetic associations implicated by rare recurrent copy number variations (CNVs). Both of these NDDs have been shown to share similar biological etiologies as well as genetic pleiotropy. Platforms aimed at investigating genetic-based associations, such as high-density microarray technologies, have been groundbreaking techniques in the field of complex diseases, aimed at elucidating the underlying disease biology. Previous studies have uncovered CNVs associated with genes within shared candidate genomic networks, including glutamate receptor genes, across multiple different NDDs. To examine shared biological pathways across two of the most common NDDs, we investigated CNVs across 15,689 individuals with ADHD (n = 7920), ASD (n = 4318), or both (n = 3,416), as well as 19,993 controls. Cases and controls were matched by genotype array (i.e., Illumina array versions). Three case-control association studies each calculated and compared the observed vs. expected frequency of CNVs across individual genes, loci, pathways, and gene networks. Quality control measures of confidence in CNV-calling, prior to association analyses, included visual inspection of genotype and hybridization intensity. Here, we report results from CNV analysis in search for individual genes, loci, pathways, and gene networks. To extend our previous observations implicating a key role of the metabotropic glutamate receptor (mGluR) network in both ADHD and autism, we exhaustively queried patients with ASD and/or ADHD for CNVs associated with the 273 genomic regions of interest within the mGluR gene network (genes with one or two degrees protein-protein interaction with mGluR 1-8 genes). Among CNVs in mGluR network genes, we uncovered CNTN4 deletions enriched in NDD cases (P = 3.22E - 26, OR = 2.49). Additionally, we uncovered PRLHR deletions in 40 ADHD cases and 12 controls (P = 5.26E - 13, OR = 8.45) as well as clinically diagnostic relevant 22q11.2 duplications and 16p11.2 duplications in 23 ADHD + ASD cases and 9 controls (P = 4.08E - 13, OR = 15.05) and 22q11.2 duplications in 34 ADHD + ASD cases and 51 controls (P = 9.21E - 9, OR = 3.93); those control samples were not with previous 22qDS diagnosis in their EHR records. Together, these results suggest that disruption in neuronal cell-adhesion pathways confers significant risk to NDDs and showcase that rare recurrent CNVs in CNTN4, 22q11.2, and 16p11.2 are overrepresented in NDDs that constitute patients predominantly suffering from ADHD and ASD.
Background Neurodevelopmental disorders (NDDs), such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are examples of complex and partially overlapping phenotypes that often lack definitive corroborating genetic information. ADHD and ASD have complex genetic associations implicated by rare recurrent copy number variations (CNVs). Both of these NDDs have been shown to share similar biological etiologies as well as genetic pleiotropy. Methods Platforms aimed at investigating genetic-based associations, such as high-density microarray technologies, have been groundbreaking techniques in the field of complex diseases, aimed at elucidating the underlying disease biology. Previous studies have uncovered CNVs associated with genes within shared candidate genomic networks, including glutamate receptor genes, across multiple different NDDs. To examine shared biological pathways across two of the most common NDDs, we investigated CNVs across 15,689 individuals with ADHD ( n  = 7920), ASD ( n  = 4318), or both ( n  = 3,416), as well as 19,993 controls. Cases and controls were matched by genotype array (i.e., Illumina array versions). Three case–control association studies each calculated and compared the observed vs. expected frequency of CNVs across individual genes, loci, pathways, and gene networks. Quality control measures of confidence in CNV-calling, prior to association analyses, included visual inspection of genotype and hybridization intensity. Results Here, we report results from CNV analysis in search for individual genes, loci, pathways, and gene networks. To extend our previous observations implicating a key role of the metabotropic glutamate receptor (mGluR) network in both ADHD and autism, we exhaustively queried patients with ASD and/or ADHD for CNVs associated with the 273 genomic regions of interest within the mGluR gene network (genes with one or two degrees protein–protein interaction with mGluR 1–8 genes). Among CNVs in mGluR network genes, we uncovered CNTN4 deletions enriched in NDD cases ( P  = 3.22E − 26, OR = 2.49). Additionally, we uncovered PRLHR deletions in 40 ADHD cases and 12 controls ( P  = 5.26E − 13, OR = 8.45) as well as clinically diagnostic relevant 22q11.2 duplications and 16p11.2 duplications in 23 ADHD + ASD cases and 9 controls ( P  = 4.08E − 13, OR = 15.05) and 22q11.2 duplications in 34 ADHD + ASD cases and 51 controls ( P  = 9.21E − 9, OR = 3.93); those control samples were not with previous 22qDS diagnosis in their EHR records. Conclusion Together, these results suggest that disruption in neuronal cell-adhesion pathways confers significant risk to NDDs and showcase that rare recurrent CNVs in CNTN4 , 22q11.2, and 16p11.2 are overrepresented in NDDs that constitute patients predominantly suffering from ADHD and ASD. Trial registration ClinicalTrials.gov Identifier: NCT02286817 First Posted: 10 November 14, ClinicalTrials.gov Identifier: NCT02777931 first posted: 19 May 2016, ClinicalTrials.gov Identifier: NCT03006367 first posted: 30 December 2016, ClinicalTrials.gov Identifier: NCT02895906 first posted: 12 September 2016.
ArticleNumber 14
Audience Academic
Author Mentch, Frank
Khan, Munir E.
Slaby, Isabella
March, Michael E.
Hain, Heather
Sleiman, Patrick M. A.
Chang, Xiao
Connolly, John
Kao, Charlly
Lemma, Maria
Hakonarson, Hakon
Otieno, F. George
Glessner, Joseph T.
Li, Jin
Liu, Yichuan
Author_xml – sequence: 1
  givenname: Joseph T.
  orcidid: 0000-0001-5131-2811
  surname: Glessner
  fullname: Glessner, Joseph T.
  organization: Center for Applied Genomics, Children’s Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania
– sequence: 2
  givenname: Munir E.
  surname: Khan
  fullname: Khan, Munir E.
  organization: Center for Applied Genomics, Children’s Hospital of Philadelphia
– sequence: 3
  givenname: Xiao
  surname: Chang
  fullname: Chang, Xiao
  organization: Center for Applied Genomics, Children’s Hospital of Philadelphia
– sequence: 4
  givenname: Yichuan
  surname: Liu
  fullname: Liu, Yichuan
  organization: Center for Applied Genomics, Children’s Hospital of Philadelphia
– sequence: 5
  givenname: F. George
  surname: Otieno
  fullname: Otieno, F. George
  organization: Center for Applied Genomics, Children’s Hospital of Philadelphia
– sequence: 6
  givenname: Maria
  surname: Lemma
  fullname: Lemma, Maria
  organization: Center for Applied Genomics, Children’s Hospital of Philadelphia
– sequence: 7
  givenname: Isabella
  surname: Slaby
  fullname: Slaby, Isabella
  organization: Center for Applied Genomics, Children’s Hospital of Philadelphia
– sequence: 8
  givenname: Heather
  surname: Hain
  fullname: Hain, Heather
  organization: Center for Applied Genomics, Children’s Hospital of Philadelphia
– sequence: 9
  givenname: Frank
  surname: Mentch
  fullname: Mentch, Frank
  organization: Center for Applied Genomics, Children’s Hospital of Philadelphia
– sequence: 10
  givenname: Jin
  surname: Li
  fullname: Li, Jin
  organization: Department of Cell Biology, the Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University
– sequence: 11
  givenname: Charlly
  surname: Kao
  fullname: Kao, Charlly
  organization: Center for Applied Genomics, Children’s Hospital of Philadelphia
– sequence: 12
  givenname: Patrick M. A.
  surname: Sleiman
  fullname: Sleiman, Patrick M. A.
  organization: Center for Applied Genomics, Children’s Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania
– sequence: 13
  givenname: Michael E.
  surname: March
  fullname: March, Michael E.
  organization: Center for Applied Genomics, Children’s Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania
– sequence: 14
  givenname: John
  surname: Connolly
  fullname: Connolly, John
  organization: Center for Applied Genomics, Children’s Hospital of Philadelphia
– sequence: 15
  givenname: Hakon
  surname: Hakonarson
  fullname: Hakonarson, Hakon
  email: hakonarson@chop.edu
  organization: Center for Applied Genomics, Children’s Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania
BackLink https://www.ncbi.nlm.nih.gov/pubmed/37120522$$D View this record in MEDLINE/PubMed
BookMark eNp9ks1q3DAUhU1JaX7aF-iiGAqlG6eSLdnWqoTQn0CgUNq1uJavPQq2NJXklOQJ-ti9mUmaTCjBCxnpO8e-R-cw23PeYZa95uyY87b-EDmvW1WwsiqYEm1VXD_LDuigLriScu_B-352GOMFY3VVSvki268aXjJZlgfZn-8QMA9olhDQpdz49VXulrnDkF9CsJCsdzG3Lp8xQedT8Gtr8nFaEsyQNlJcJx8ISRjAJOvGfESHG5FZ2akn4_y3Tavc4RJ8j5c4-fVMX4Mp7230occQX2bPB5givrpdj7Kfnz_9OP1anH_7cnZ6cl6YulKp4FXPa1MqbETHyl4gp5GGqm4BZNl2RgFjEqXpRFM3Vd2pGjoleuCyQahkVx1lZ1vf3sOFXgc7Q7jSHqzebPgwagjJmgl1R9GxWpSDEiBUy9TQokBRd_0gBwk9eX3ceq2Xbsbe0EgBph3T3RNnV3r0l5ozLlohFDm8v3UI_teCMenZRoPTBA79EnXZskbxRkpO6NtH6IVfgqOsiOKylow17T01Ak1g3UA3BubGVJ80opEUS9sQdfwfip4eZ2uoZYOl_R3BuweCFcKUVtFTCW7asQu-eRjJvyzuGkdAuwVM8DEGHLSxadMy-gU7UTT6ptx6W25N5dabcutrkpaPpHfuT4qqrSgS7EYM97E9ofoLZG4Oog
CitedBy_id crossref_primary_10_1159_000534123
crossref_primary_10_1186_s11689_024_09526_z
crossref_primary_10_1016_j_pnpbp_2024_111107
crossref_primary_10_1021_acsomega_4c05522
crossref_primary_10_1016_j_neuropharm_2024_109897
Cites_doi 10.1126/science.1138659
10.1038/nature07953
10.1101/gr.248682.119
10.1016/j.biopsych.2020.12.028
10.1093/nar/gks1346
10.1038/s41398-021-01763-3
10.1038/s41467-019-13624-1
10.1001/jamapsychiatry.2014.2650
10.1001/archpsyc.61.7.649
10.1007/7854_2011_179
10.1097/DBP.0000000000000065
10.1038/nrg3871
10.1016/j.gep.2020.119097
10.1038/ejhg.2015.269
10.1038/tp.2016.273
10.1038/ng.1013
10.1002/ajmg.b.30869
10.1016/j.pharmthera.2018.05.007
10.1016/j.brainres.2006.09.011
10.1038/s41398-019-0599-y
10.1016/j.neubiorev.2012.11.013
10.3389/fphar.2012.00159
10.1038/srep19372
10.1186/1755-8166-6-11
10.1016/j.celrep.2018.08.022
10.1016/j.jad.2015.10.004
10.3390/jcm10071475
10.1038/s41398-021-01223-y
10.1002/gepi.20303
10.1093/bib/bbaa381
10.1038/s41467-017-02244-2
10.1093/bioinformatics/btw477
10.1016/j.neuron.2010.01.016
10.1002/ajmg.b.32253
10.1016/j.neuropharm.2017.04.037
10.1038/sj.npp.1301312
10.1038/ng.474
10.1038/s41586-020-2287-8
10.1016/j.ijcard.2019.07.058
10.1007/s13760-021-01605-5
10.1101/gr.5402306
10.1503/jpn.130242
10.1038/sj.mp.4001940
10.1034/j.1399-5618.2003.00024.x
10.1186/s11689-022-09447-9
10.1101/gr.6861907
10.3389/fpsyt.2018.00767
10.1038/s41431-022-01222-7
10.1093/hmg/ddv436
10.1038/ncomms5074
ContentType Journal Article
Copyright The Author(s) 2023
2023. The Author(s).
COPYRIGHT 2023 BioMed Central Ltd.
2023. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
Copyright_xml – notice: The Author(s) 2023
– notice: 2023. The Author(s).
– notice: COPYRIGHT 2023 BioMed Central Ltd.
– notice: 2023. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
DBID C6C
AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
3V.
7RV
7TK
7X7
7XB
88E
8FD
8FI
8FJ
8FK
ABUWG
AFKRA
AZQEC
BENPR
CCPQU
DWQXO
FR3
FYUFA
GHDGH
K9.
KB0
M0S
M1P
NAPCQ
P64
PHGZM
PHGZT
PIMPY
PJZUB
PKEHL
PPXIY
PQEST
PQQKQ
PQUKI
PRINS
PSYQQ
RC3
7X8
5PM
DOA
DOI 10.1186/s11689-023-09483-z
DatabaseName SpringerOpen Free (Free internet resource, activated by CARLI)
CrossRef
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
ProQuest Central (Corporate)
Nursing & Allied Health Database
Neurosciences Abstracts
Health & Medical Collection
ProQuest Central (purchase pre-March 2016)
Medical Database (Alumni Edition)
Technology Research Database
Hospital Premium Collection
Hospital Premium Collection (Alumni Edition)
ProQuest Central (Alumni) (purchase pre-March 2016)
ProQuest Central (Alumni)
ProQuest Central UK/Ireland
ProQuest Central Essentials
ProQuest Central
ProQuest One
ProQuest Central Korea
Engineering Research Database
Proquest Health Research Premium Collection
Health Research Premium Collection (Alumni)
ProQuest Health & Medical Complete (Alumni)
Nursing & Allied Health Database (Alumni Edition)
ProQuest Health & Medical Collection
Medical Database
Nursing & Allied Health Premium
Biotechnology and BioEngineering Abstracts
Proquest Central Premium
ProQuest One Academic (New)
Publicly Available Content Database
ProQuest Health & Medical Research Collection
ProQuest One Academic Middle East (New)
ProQuest One Health & Nursing
ProQuest One Academic Eastern Edition (DO NOT USE)
ProQuest One Academic
ProQuest One Academic UKI Edition
ProQuest Central China
ProQuest One Psychology
Genetics Abstracts
MEDLINE - Academic
PubMed Central (Full Participant titles)
DOAJ Directory of Open Access Journals
DatabaseTitle CrossRef
MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
Publicly Available Content Database
ProQuest One Psychology
Technology Research Database
ProQuest One Academic Middle East (New)
ProQuest Central Essentials
ProQuest Health & Medical Complete (Alumni)
ProQuest Central (Alumni Edition)
ProQuest One Community College
ProQuest One Health & Nursing
ProQuest Central China
ProQuest Central
Genetics Abstracts
Health Research Premium Collection
Health and Medicine Complete (Alumni Edition)
ProQuest Central Korea
Health & Medical Research Collection
ProQuest Central (New)
ProQuest Medical Library (Alumni)
ProQuest One Academic Eastern Edition
ProQuest Nursing & Allied Health Source
ProQuest Hospital Collection
Health Research Premium Collection (Alumni)
Neurosciences Abstracts
ProQuest Hospital Collection (Alumni)
Biotechnology and BioEngineering Abstracts
Nursing & Allied Health Premium
ProQuest Health & Medical Complete
ProQuest Medical Library
ProQuest One Academic UKI Edition
ProQuest Nursing & Allied Health Source (Alumni)
Engineering Research Database
ProQuest One Academic
ProQuest One Academic (New)
ProQuest Central (Alumni)
MEDLINE - Academic
DatabaseTitleList
MEDLINE - Academic
MEDLINE
Publicly Available Content Database




Database_xml – sequence: 1
  dbid: C6C
  name: Springer Nature OA Free Journals
  url: http://www.springeropen.com/
  sourceTypes: Publisher
– sequence: 2
  dbid: DOA
  name: DOAJ Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 3
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 4
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
– sequence: 5
  dbid: BENPR
  name: ProQuest Central
  url: http://www.proquest.com/pqcentral?accountid=15518
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Medicine
Biology
EISSN 1866-1955
EndPage 11
ExternalDocumentID oai_doaj_org_article_b1950642f94a49809f8e4e46bdf5f5ad
PMC10148449
A747547687
37120522
10_1186_s11689_023_09483_z
Genre Research Support, Non-U.S. Gov't
Journal Article
Research Support, N.I.H., Extramural
GrantInformation_xml – fundername: Eunice Kennedy Shriver National Institute of Child Health and Human Development
  grantid: U54-HD086984
  funderid: http://dx.doi.org/10.13039/100009633
– fundername: National Human Genome Research Institute
  grantid: 5U01HG011175-03; U01-HG006830
  funderid: http://dx.doi.org/10.13039/100000051
– fundername: NICHD NIH HHS
  grantid: U54 HD086984
– fundername: NHGRI NIH HHS
  grantid: U01-HG006830
– fundername: NHGRI NIH HHS
  grantid: U01 HG011175
– fundername: NICHD NIH HHS
  grantid: P50 HD105354
– fundername: ;
  grantid: 5U01HG011175-03; U01-HG006830
– fundername: ;
  grantid: U54-HD086984
GroupedDBID 0R~
29L
2JY
4.4
53G
5GY
5VS
67Z
6NX
7RV
7X7
88E
8FI
8FJ
AAFWJ
AAJSJ
AASML
ABIVO
ABUWG
ACGFS
ACPRK
ADBBV
ADRAZ
ADUKV
AENEX
AFKRA
AFPKN
AHBYD
AHMBA
AHYZX
ALMA_UNASSIGNED_HOLDINGS
AMKLP
AOIJS
BA0
BAPOH
BCNDV
BENPR
BFQNJ
BMC
BPHCQ
BVXVI
C6C
CAG
CCPQU
CSCUP
DU5
EBLON
EBS
EMOBN
F5P
FEDTE
FYUFA
GROUPED_DOAJ
GXS
HMCUK
HVGLF
HYE
IAO
IHR
IHW
INH
INR
IPY
ITC
IXC
I~X
KOV
KQ8
M1P
M48
NAPCQ
O9I
OK1
P2P
PGMZT
PHGZM
PHGZT
PIMPY
PJZUB
PPXIY
PQQKQ
PROAC
PSQYO
PSYQQ
PUEGO
QOS
RBZ
RNS
ROL
RPM
RSV
S27
SDH
SMD
SOJ
T13
U2A
UKHRP
VC2
WK8
AAYXX
ALIPV
CITATION
-5E
-5G
-A0
-BR
3V.
ACRMQ
ADINQ
C24
CGR
CUY
CVF
ECM
EIF
HG6
M~E
NPM
PMFND
7TK
7XB
8FD
8FK
AZQEC
DWQXO
FR3
K9.
P64
PKEHL
PQEST
PQUKI
PRINS
RC3
7X8
5PM
ID FETCH-LOGICAL-c639t-13d16c29e74b02d4e1325f368aa528bc9a005e5cb476736b96ab94da157ea35b3
IEDL.DBID M48
ISSN 1866-1955
1866-1947
IngestDate Wed Aug 27 01:19:50 EDT 2025
Thu Aug 21 18:38:01 EDT 2025
Fri Sep 05 04:58:22 EDT 2025
Fri Jul 25 05:11:57 EDT 2025
Tue Jun 17 21:38:12 EDT 2025
Tue Jun 10 20:45:20 EDT 2025
Thu May 22 21:18:48 EDT 2025
Thu Jan 02 22:40:30 EST 2025
Tue Jul 01 02:30:42 EDT 2025
Thu Apr 24 22:53:16 EDT 2025
Sat Sep 06 07:21:25 EDT 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 1
Keywords Genetic association study
Autism
Metabotropic glutamate receptors
Copy number variation
Neurodevelopmental disorders
Attention-deficit/hyperactivity disorder
Language English
License 2023. The Author(s).
Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c639t-13d16c29e74b02d4e1325f368aa528bc9a005e5cb476736b96ab94da157ea35b3
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ORCID 0000-0001-5131-2811
OpenAccessLink http://journals.scholarsportal.info/openUrl.xqy?doi=10.1186/s11689-023-09483-z
PMID 37120522
PQID 2815650078
PQPubID 2040182
PageCount 11
ParticipantIDs doaj_primary_oai_doaj_org_article_b1950642f94a49809f8e4e46bdf5f5ad
pubmedcentral_primary_oai_pubmedcentral_nih_gov_10148449
proquest_miscellaneous_2807917551
proquest_journals_2815650078
gale_infotracmisc_A747547687
gale_infotracacademiconefile_A747547687
gale_healthsolutions_A747547687
pubmed_primary_37120522
crossref_citationtrail_10_1186_s11689_023_09483_z
crossref_primary_10_1186_s11689_023_09483_z
springer_journals_10_1186_s11689_023_09483_z
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate 2023-04-29
PublicationDateYYYYMMDD 2023-04-29
PublicationDate_xml – month: 04
  year: 2023
  text: 2023-04-29
  day: 29
PublicationDecade 2020
PublicationPlace London
PublicationPlace_xml – name: London
– name: England
PublicationTitle Journal of neurodevelopmental disorders
PublicationTitleAbbrev J Neurodevelop Disord
PublicationTitleAlternate J Neurodev Disord
PublicationYear 2023
Publisher BioMed Central
BioMed Central Ltd
BMC
Publisher_xml – name: BioMed Central
– name: BioMed Central Ltd
– name: BMC
References J Elia (9483_CR10) 2011; 44
9483_CR26
C RegioBrambilla (9483_CR43) 2022; 12
JT Glessner (9483_CR20) 2009; 459
TL Wenger (9483_CR12) 2016; 6
K Wang (9483_CR2) 2007; 17
J Wang (9483_CR28) 2020; 35
W Demaerel (9483_CR8) 2019; 29
9483_CR21
CT Li (9483_CR34) 2018; 9
J Lasky-Su (9483_CR27) 2008; 147B
J Elia (9483_CR42) 2018; 9
SR Sharma (9483_CR32) 2018; 190
RL Collins (9483_CR4) 2020; 581
OO Gudmundsson (9483_CR18) 2019; 9
J Sebat (9483_CR22) 2007; 316
B Sun (9483_CR25) 2022; 122
I Slaby (9483_CR16) 2022; 14
YR Li (9483_CR6) 2020; 11
CF Bruinsma (9483_CR46) 2016; 25
C Bellone (9483_CR47) 2012; 3
J Naaijen (9483_CR15) 2017; 7
D Hadley (9483_CR13) 2014; 5
Q Qi (9483_CR30) 2013; 6
JT Glessner (9483_CR3) 2013; 41
RH Bitsko (9483_CR39) 2014; 35
M Mereu (9483_CR23) 2017; 121
C Luscher (9483_CR48) 2010; 65
TU Woo (9483_CR37) 2004; 61
CE McOmish (9483_CR44) 2016; 190
N Matosin (9483_CR45) 2014; 39
I Kushima (9483_CR29) 2018; 24
A Oguro-Ando (9483_CR19) 2021; 11
W Kryszkowski (9483_CR33) 2021; 10
JT Glessner (9483_CR11) 2012; 12
JT Glessner (9483_CR49) 2021; 22
E Scarr (9483_CR38) 2003; 5
ME Hirschtritt (9483_CR41) 2015; 72
I Pe'er (9483_CR51) 2008; 32
RE McCullumsmith (9483_CR35) 2007; 1127
JT Glessner (9483_CR7) 2020; 298
SE McCarthy (9483_CR17) 2009; 41
K Cheslack-Postava (9483_CR24) 2007; 12
DA Peiffer (9483_CR1) 2006; 16
M Beneyto (9483_CR36) 2007; 32
SC Cohen (9483_CR40) 2013; 37
J Fadista (9483_CR50) 2016; 24
GC Akutagava-Martins (9483_CR14) 2014; 165B
A Mace (9483_CR5) 2016; 32
Z Yang (9483_CR31) 2021; 90
M Zarrei (9483_CR9) 2015; 16
References_xml – volume: 316
  start-page: 445
  issue: 5823
  year: 2007
  ident: 9483_CR22
  publication-title: Science
  doi: 10.1126/science.1138659
– volume: 459
  start-page: 569
  issue: 7246
  year: 2009
  ident: 9483_CR20
  publication-title: Nature
  doi: 10.1038/nature07953
– volume: 29
  start-page: 1389
  issue: 9
  year: 2019
  ident: 9483_CR8
  publication-title: Genome Res
  doi: 10.1101/gr.248682.119
– volume: 90
  start-page: 317
  issue: 5
  year: 2021
  ident: 9483_CR31
  publication-title: Biol Psychiatry
  doi: 10.1016/j.biopsych.2020.12.028
– volume: 41
  issue: 5
  year: 2013
  ident: 9483_CR3
  publication-title: Nucleic Acids Res
  doi: 10.1093/nar/gks1346
– volume: 12
  start-page: 6
  issue: 1
  year: 2022
  ident: 9483_CR43
  publication-title: Transl Psychiatry
  doi: 10.1038/s41398-021-01763-3
– volume: 11
  start-page: 255
  issue: 1
  year: 2020
  ident: 9483_CR6
  publication-title: Nat Commun
  doi: 10.1038/s41467-019-13624-1
– volume: 72
  start-page: 325
  issue: 4
  year: 2015
  ident: 9483_CR41
  publication-title: JAMA Psychiat
  doi: 10.1001/jamapsychiatry.2014.2650
– volume: 61
  start-page: 649
  issue: 7
  year: 2004
  ident: 9483_CR37
  publication-title: Arch Gen Psychiatry
  doi: 10.1001/archpsyc.61.7.649
– volume: 12
  start-page: 345
  year: 2012
  ident: 9483_CR11
  publication-title: Curr Top Behav Neurosci
  doi: 10.1007/7854_2011_179
– volume: 35
  start-page: 317
  issue: 5
  year: 2014
  ident: 9483_CR39
  publication-title: J Dev Behav Pediatr
  doi: 10.1097/DBP.0000000000000065
– volume: 16
  start-page: 172
  issue: 3
  year: 2015
  ident: 9483_CR9
  publication-title: Nat Rev Genet
  doi: 10.1038/nrg3871
– volume: 35
  year: 2020
  ident: 9483_CR28
  publication-title: Gene Expr Patterns
  doi: 10.1016/j.gep.2020.119097
– volume: 24
  start-page: 1202
  issue: 8
  year: 2016
  ident: 9483_CR50
  publication-title: Eur J Hum Genet
  doi: 10.1038/ejhg.2015.269
– volume: 7
  start-page: e999
  issue: 1
  year: 2017
  ident: 9483_CR15
  publication-title: Transl Psychiatry
  doi: 10.1038/tp.2016.273
– volume: 44
  start-page: 78
  issue: 1
  year: 2011
  ident: 9483_CR10
  publication-title: Nat Genet
  doi: 10.1038/ng.1013
– volume: 147B
  start-page: 1355
  issue: 8
  year: 2008
  ident: 9483_CR27
  publication-title: Am J Med Genet B Neuropsychiatr Genet
  doi: 10.1002/ajmg.b.30869
– volume: 190
  start-page: 91
  year: 2018
  ident: 9483_CR32
  publication-title: Pharmacol Ther
  doi: 10.1016/j.pharmthera.2018.05.007
– volume: 1127
  start-page: 108
  issue: 1
  year: 2007
  ident: 9483_CR35
  publication-title: Brain Res
  doi: 10.1016/j.brainres.2006.09.011
– volume: 9
  start-page: 258
  issue: 1
  year: 2019
  ident: 9483_CR18
  publication-title: Transl Psychiatry
  doi: 10.1038/s41398-019-0599-y
– volume: 37
  start-page: 997
  issue: 6
  year: 2013
  ident: 9483_CR40
  publication-title: Neurosci Biobehav Rev
  doi: 10.1016/j.neubiorev.2012.11.013
– volume: 3
  start-page: 159
  year: 2012
  ident: 9483_CR47
  publication-title: Front Pharmacol
  doi: 10.3389/fphar.2012.00159
– volume: 6
  start-page: 19372
  year: 2016
  ident: 9483_CR12
  publication-title: Sci Rep
  doi: 10.1038/srep19372
– volume: 6
  start-page: 11
  issue: 1
  year: 2013
  ident: 9483_CR30
  publication-title: Mol Cytogenet
  doi: 10.1186/1755-8166-6-11
– volume: 24
  start-page: 2838
  issue: 11
  year: 2018
  ident: 9483_CR29
  publication-title: Cell Rep
  doi: 10.1016/j.celrep.2018.08.022
– volume: 190
  start-page: 241
  year: 2016
  ident: 9483_CR44
  publication-title: J Affect Disord
  doi: 10.1016/j.jad.2015.10.004
– volume: 10
  start-page: 1475
  issue: 7
  year: 2021
  ident: 9483_CR33
  publication-title: J Clin Med
  doi: 10.3390/jcm10071475
– volume: 11
  start-page: 106
  issue: 1
  year: 2021
  ident: 9483_CR19
  publication-title: Transl Psychiatry
  doi: 10.1038/s41398-021-01223-y
– volume: 32
  start-page: 381
  issue: 4
  year: 2008
  ident: 9483_CR51
  publication-title: Genet Epidemiol
  doi: 10.1002/gepi.20303
– volume: 22
  start-page: 381
  issue: 5
  year: 2021
  ident: 9483_CR49
  publication-title: Brief Bioinform
  doi: 10.1093/bib/bbaa381
– volume: 9
  start-page: 4
  issue: 1
  year: 2018
  ident: 9483_CR42
  publication-title: Nat Commun
  doi: 10.1038/s41467-017-02244-2
– volume: 32
  start-page: 3298
  issue: 21
  year: 2016
  ident: 9483_CR5
  publication-title: Bioinformatics
  doi: 10.1093/bioinformatics/btw477
– volume: 65
  start-page: 445
  issue: 4
  year: 2010
  ident: 9483_CR48
  publication-title: Neuron
  doi: 10.1016/j.neuron.2010.01.016
– volume: 165B
  start-page: 502
  issue: 6
  year: 2014
  ident: 9483_CR14
  publication-title: Am J Med Genet B Neuropsychiatr Genet
  doi: 10.1002/ajmg.b.32253
– volume: 121
  start-page: 179
  year: 2017
  ident: 9483_CR23
  publication-title: Neuropharmacology
  doi: 10.1016/j.neuropharm.2017.04.037
– volume: 32
  start-page: 1888
  issue: 9
  year: 2007
  ident: 9483_CR36
  publication-title: Neuropsychopharmacology
  doi: 10.1038/sj.npp.1301312
– volume: 41
  start-page: 1223
  issue: 11
  year: 2009
  ident: 9483_CR17
  publication-title: Nat Genet
  doi: 10.1038/ng.474
– volume: 581
  start-page: 444
  issue: 7809
  year: 2020
  ident: 9483_CR4
  publication-title: Nature
  doi: 10.1038/s41586-020-2287-8
– volume: 298
  start-page: 107
  year: 2020
  ident: 9483_CR7
  publication-title: Int J Cardiol
  doi: 10.1016/j.ijcard.2019.07.058
– volume: 122
  start-page: 1169
  issue: 5
  year: 2022
  ident: 9483_CR25
  publication-title: Acta Neurol Belg
  doi: 10.1007/s13760-021-01605-5
– volume: 16
  start-page: 1136
  issue: 9
  year: 2006
  ident: 9483_CR1
  publication-title: Genome Res
  doi: 10.1101/gr.5402306
– volume: 39
  start-page: 407
  issue: 6
  year: 2014
  ident: 9483_CR45
  publication-title: J Psychiatry Neurosci
  doi: 10.1503/jpn.130242
– volume: 12
  start-page: 283
  issue: 3
  year: 2007
  ident: 9483_CR24
  publication-title: Mol Psychiatry
  doi: 10.1038/sj.mp.4001940
– volume: 5
  start-page: 257
  issue: 4
  year: 2003
  ident: 9483_CR38
  publication-title: Bipolar Disord
  doi: 10.1034/j.1399-5618.2003.00024.x
– volume: 14
  start-page: 37
  issue: 1
  year: 2022
  ident: 9483_CR16
  publication-title: J Neurodev Disord
  doi: 10.1186/s11689-022-09447-9
– volume: 17
  start-page: 1665
  issue: 11
  year: 2007
  ident: 9483_CR2
  publication-title: Genome Res
  doi: 10.1101/gr.6861907
– ident: 9483_CR26
– volume: 9
  start-page: 767
  year: 2018
  ident: 9483_CR34
  publication-title: Front Psychiatry
  doi: 10.3389/fpsyt.2018.00767
– ident: 9483_CR21
  doi: 10.1038/s41431-022-01222-7
– volume: 25
  start-page: 1
  issue: 1
  year: 2016
  ident: 9483_CR46
  publication-title: Hum Mol Genet
  doi: 10.1093/hmg/ddv436
– volume: 5
  start-page: 4074
  year: 2014
  ident: 9483_CR13
  publication-title: Nat Commun
  doi: 10.1038/ncomms5074
SSID ssj0063255
Score 2.3316474
Snippet Background Neurodevelopmental disorders (NDDs), such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are examples of...
Neurodevelopmental disorders (NDDs), such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are examples of complex and...
Background Neurodevelopmental disorders (NDDs), such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are examples of...
BackgroundNeurodevelopmental disorders (NDDs), such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are examples of...
Abstract Background Neurodevelopmental disorders (NDDs), such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are...
SourceID doaj
pubmedcentral
proquest
gale
pubmed
crossref
springer
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage 14
SubjectTerms Adrenergic receptors
Analysis
Attention deficit hyperactivity disorder
Autism
Autism Spectrum Disorder - genetics
Biology
Biomedical and Life Sciences
Biomedicine
Cell adhesion & migration
Copy number
Copy number variation
Disease
DNA Copy Number Variations - genetics
DNA microarrays
Gene loci
Genes
Genetic aspects
Genetic association study
Genetic Predisposition to Disease
Genetic research
Genome-Wide Association Study
Genomics
Genotypes
Glutamate
Glutamic acid receptors (metabotropic)
Human Genetics
Humans
Hybridization
IDDRC 2023
Ligands
Medical research
Medicine, Experimental
Metabotropic glutamate receptors
Neurodevelopmental disorders
Neurology
Neuropsychology
Neurosciences
Pathophysiology
Pediatrics
Phenotypes
Pleiotropy
Protein-protein interactions
Proteins
Psychiatry
Quality control
Receptors, Metabotropic Glutamate - genetics
SummonAdditionalLinks – databaseName: DOAJ Directory of Open Access Journals
  dbid: DOA
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Lb9QwELZQD4gL4k2ggJGQOEDUJH7EPhZEVSGVA6JSb5ZfWVai2dXuFqn9Bf3ZzNjJtikCLlzjseTMjMcz9sw3hLzh3joVIy91YKzkzstSR4dP7Ir5mgdQASxOPvoiD4_55xNxcq3VF-aEZXjgzLg9h31KwUnuNLdcq0p3KvLIpQud6IQNaH0rXY3BVLbBkoGnPJbIKLm3rmuJqUENKyGcUay8mBxDCa3_d5t87VC6mTB549U0HUYH98jdwYuk-3n198mt2D8gt4-Gd_KH5PKrXUW6wrt0RF-ifrE8p7n5B_0J0XG-pqPznp7GDajBZrVYzj2dgRpacGHT1LiEcJwinEQqpOpndIZ2ESeNFeAUb3FpgsQMV8lHsLAwYHquH5Hjg0_fPh6WQ8-F0oOvgp3pQy19o2PLXdUEHiFaFR2TylrRKOe1hW0bhXe8xYwwp6V1mgdbizZaJhx7THb6RR-fEtpVcPI1PHgXFASdSlmlve20Ag9NxkoWpB5FYPwASI59MX6YFJgoabLYDIjNJLGZi4K8285ZZjiOv1J_QMluKRFKO30ABTODgpl_KVhBXqFemFyXujUIZh8CMQFcUG1B3iYKNAnwA94OlQ3ABgTXmlDuTihhK_vp8Kh7ZjAla9Mgno9AV64gr7fDOBPT4_q4OEOaqoW4G7zfgjzJqrr9adbWTQVedkHURIknXJmO9PPvCWgc-ziD6HRB3o_6frWuP7P92f9g-3Nyp0n7lZeN3iU7m9VZfAH-38a9TFv9F66lWS4
  priority: 102
  providerName: Directory of Open Access Journals
– databaseName: Health & Medical Collection
  dbid: 7X7
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1Lb9QwELagCNQLgvJooICRkDhA1Dwcxz6hgqgqpHJAVNqb5VeWlSBZdrdI7S_gZzPjOFlSRK_xWIo9D8_YM98Q8opZbYT3LJWuLFNmLE-lN_jELkqbMwcigMXJp5_5yRn7NKtm8cJtHdMqB5sYDLXrLN6RHxYIa1LhifZu-TPFrlH4uhpbaNwkt3LwRLB1Qz0bAy5eFqHrKWK6pRCs10PRjOCH6zznmCxUlCkEOKJMLycHU8Dv_9dK_3VMXU2hvPKOGo6n43vkbvQr6VEvCPfJDd_ukdt9p8mLPXLnNL6hPyC_v-iVpyu8Z0dkJmq75QXtG4PQXxA591d4dNHSH34DIrJZdcuFpXMQUQ3ubZjqlxCqU4SaCEVW7ZzO0WbipKE6nOINLw1wmW6bmAS_6CLe5_ohOTv--PXDSRr7MaQW_BjsWu9ybgvpa2aywjEPkWzVlFxoXRXCWKlBpX1lDasxW8xIro1kTudV7XVZmfIR2Wm71u8T2mRwKhbMWeMEBKRCaCGtbqQA7437jCckH5ihbAQrx54Z31UIWgRXPQMVMFAFBqrLhLwZ5yx7qI5rqd8jj0dKhNkOH7rVXEWtVQab5EKE1kimmRSZbIRnnnHjmqqptEvIC5QQ1desjsZCHUGQVsEuiDohrwMFmgtYgNWx6gG2AYG3JpQHE0pQczsdHqRQRTOzVlulSMjLcRhnYupc67tzpMlqiMnBM07I415ox0WXdV5k4IEnREzEebIr05F28S2AkGOPZ2CdTMjbQfK3__X_bX9y_TKekt0i6CRLC3lAdjarc_8MvL6NeR5U-w_A-1U9
  priority: 102
  providerName: ProQuest
– databaseName: SpringerOpen Free (Free internet resource, activated by CARLI)
  dbid: C6C
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV1baxUxEA5aQXwR726tGkHwQRd3N5dNHuvBUoT6IBb6FnLb44G653DOqdD-An-2M9lLu_UCvm5mIJuZTGaSmW8Iec29dSpGnuvAWM6dl7mODp_YFfMlD6ACWJx89FkeHvNPJ-Kkh8nBWpir7_elku83ZSkxqadiOQQiiuUXN8ktAYYXtXkmZ4PVlQx846Eo5o98k4Mn4fP_boWvHEPXUySvvZOm4-fgHrnb-410vxP0fXIjtg_I7aP-Zfwh-fnFriNd4-054i1Rv1yd067dB_0B8XB3MUcXLf0etyD47Xq5Wng6B8Wz4LQm1riCAJwigEQqnWrndI6WEJmGmm-K97Y0gWCGy3QjmFjoUTw3j8jxwcevs8O877KQe_BOsBd9KKWvdKy5K6rAI8SnomFSWSsq5by2sFGj8I7XmAPmtLRO82BLUUfLhGOPyU67bONTQpsCzrqKB--CgjBTKau0t41W4JPJWMiMlIMIjO8hyLETxqlJoYiSphObAbGZJDZzkZG3I8-qA-D4J_UHlOxIieDZ6QPolOn3onHY-hbirkZzy7UqdKMij1y60IhG2JCRl6gXpqtEHU2A2YfQS8AqqDojbxIFGgH4AW_7WgZYBoTTmlDuTShh8_rp8KB7pjceG1Mhgo9A5y0jr8Zh5MSEuDYuz5CmqCHSBn83I086VR1_mtVlVYBfnRE1UeLJqkxH2sW3BC2OnZtBdDoj7wZ9v5zX35d99__In5E7VdqZPK_0HtnZrs_ic_Dttu5F2tS_AEnGSes
  priority: 102
  providerName: Springer Nature
Title Rare recurrent copy number variations in metabotropic glutamate receptor interacting genes in children with neurodevelopmental disorders
URI https://link.springer.com/article/10.1186/s11689-023-09483-z
https://www.ncbi.nlm.nih.gov/pubmed/37120522
https://www.proquest.com/docview/2815650078
https://www.proquest.com/docview/2807917551
https://pubmed.ncbi.nlm.nih.gov/PMC10148449
https://doaj.org/article/b1950642f94a49809f8e4e46bdf5f5ad
Volume 15
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV3da9swEBf9gNKXse956zINBnvYvNqyLEsPY6ShpQxaRlkgb0aS5SzQOZmTjrV_wf7s3cl2OnftXgy2TiDrfifdSfdByBtutZHO8VAVSRJyY0WonMErdpnYmBcAAQxOPjkVx2P-eZJONkhX7qidwOWtph3WkxrX5x9-_bj8BAL_0Qu8FPvLOBbo-MOSEIwVmYRXm2Tb3xehKx9f3yqIBPTnLnDm1n67ZCfJYhaljPX2KZ_O_99F-69d66ZH5Y1rVb9bHd0n91o1kw4bXDwgG656SHZO2ov0R-T3ma4drfGwHdMzUTtfXNKmOgj9CeZzc45HZxX97laAk1U9X8wsnQJONei4vqtbgL1OMd-Ej7SqpnSKCyd26kLEKR7zUp8zs7j2ToKBFW3Sz-VjMj46_Do6DtuiDKEFZQZL1xexsEy5jJuIFdyBOZuWiZBap0waqzTItUut4Rm6jBkltFG80HGaOZ2kJnlCtqp55Z4RWkawNTJeWFNIsEql1FJZXSoJKpxwkQhI3LEgt23GciyccZ57y0WKvOFgDhzMPQfzq4C8W_dZNPk6_kt9gJxdU2Kubf9hXk_zVnRzg5VywUwrFddcyUiV0nHHhSnKtEx1EZBXiIu8CVxdrxj5ECy1FGZBZgF56ykQxfADVrehDzANmH2rR7nXowRZt_3mDnt5Jyo5w4Q_Kep6AXm9bsae6D9XufkF0kQZGOagHgfkaQPV9U93iA-I7IG4Nyv9lmr2zWcix0LPwDoVkPcd3q_Hdfe0P79zDC_ILvPyyEOm9sjWqr5wL0HrW5kB2cwm2YBsHxyefjmDt5EYDfwJysALOTzHbPgHjApY4g
linkProvider Scholars Portal
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9QwELZKEY8LgvIKFGokEAeImoeT2AeEyqPa0m4PqJX25tqOs6wEyZLdgra_gF_Db2TGSXZJEb31Go-jxDOehz3zDSHPmVGaW8t8kcexz7RJfWE1XrHz2IQsBxHA4uThYTo4Zp9GyWiN_O5qYTCtstOJTlHnlcEz8u0IYU0StGhvp9997BqFt6tdC41GLPbt4ieEbLM3ex-Avy-iaPfj0fuB33YV8A1YY-y9noepiYTNmA6inFmIx5IiTrlSScS1EQoE0yZGswxznrRIlRYsV2GSWRUnOob3XiFXGV4xwv7JRssAL4UXYcokYsj5oWBZV6TD0-1ZGKaYnBTFPgRUPPbPeobQ9Qv41yr8ZRbPp2yeu7d15nD3NrnV-rF0pxG8O2TNlhvkWtPZcrFBrg_bO_u75NdnVVta47k-IkFRU00XtGlEQn9ApN4cGdJJSb_ZOYjkvK6mE0PHsCUUuNNuqp3Oq5oitIUr6irHdIw6Gid11egUT5Spg-fMV4lQ8Il5iy86u0eOL4VT98l6WZX2IaFFAFY4YrnROYcAmHPFhVGF4OAtpjZIPRJ2zJCmBUfHHh1fpQuSeCobBkpgoHQMlGceebWcM22gQS6kfoc8XlIirLd7UNVj2WoJqbEpL0SEhWCKCR6IgltmWarzIikSlXtkCyVENjWyS-UkdyAoTGAVeOaRl44C1RP8gFFtlQUsAwJ99Sg3e5SgVkx_uJNC2aq1mVxtQo88Ww7jTEzVK211ijRBJsApTUKPPGiEdvnTcRZGAXj8HuE9ce6tSn-knHxxoOfYUxpYJzzyupP81Xf9f9kfXfwbW-TG4Gh4IA_2Dvcfk5uR25_Mj8QmWZ_Xp_YJeJxz_dRtc0pOLluv_AGg8pF6
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV1Zb9QwELagSBUvqJwNLdRISDxA1ByOYz8ux6ocrRBipb5ZvrKsBNlod4tEfwE_mxnnaFMOidd4LDmewzP2zDeEPGVWG-E9i6XL85gZy2PpDT6xi9ymzIEIYHHy8Qk_mrF3p8XppSr-kO3eP0m2NQ2I0lRvDhtXtSou-OE6TTmm-mR5DOGJyOPz6-QGg7Mak7pm2aS3xTwHj7kvlfnjvNFxFFD7f7fNlw6nq4mTV15Pw6E03SG3Om-STlr23ybXfH2HbB937-V3yc9PeuXpCu_UEYWJ2mXzg7ZNQOh3iJLb6zq6qOk3vwFx2KyWzcLSOYijBlc2TPUNhOUUYSVCQVU9p3O0jziprwSneJtLAzSmu0hCgoW5DttzfY_Mpm8-vzqKu94LsQWfBTvUu5TbTPqSmSRzzEPUWlQ5F1oXmTBWalBfX1jDSswMM5JrI5nTaVF6nRcmv0-26mXtdwmtEjgBM-ascQKCTyG0kFZXUoCnxn3CI5L2LFC2AybH_hhfVQhQBFct2xSwTQW2qfOIPB_mNC0sxz-pXyJnB0qE1A4flqu56jRUGWyIC9FYJZlmUiSyEp55xo2riqrQLiIHKBeqrU8dDIOaQEBWwC6IMiLPAgWaBvgBq7sKB9gGBNkaUe6PKEGl7Xi4lz3VmZS1yhDXp0CXLiJPhmGciWlytV-eIU1SQvwNXnBEHrSiOvx0XqZZAt52RMRIiEe7Mh6pF18C4Dj2cwbWyYi86OX9Yl1_3_aH_0d-QLY_vp6qD29P3u-Rm1lQUhZncp9sbVZn_hE4fxvzOOj3L8ZVVUA
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Rare+recurrent+copy+number+variations+in+metabotropic+glutamate+receptor+interacting+genes+in+children+with+neurodevelopmental+disorders&rft.jtitle=Journal+of+neurodevelopmental+disorders&rft.au=Glessner%2C+Joseph+T&rft.au=Khan%2C+Munir+E&rft.au=Chang%2C+Xiao&rft.au=Liu%2C+Yichuan&rft.date=2023-04-29&rft.eissn=1866-1955&rft.volume=15&rft.issue=1&rft.spage=14&rft_id=info:doi/10.1186%2Fs11689-023-09483-z&rft_id=info%3Apmid%2F37120522&rft.externalDocID=37120522
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1866-1955&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1866-1955&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1866-1955&client=summon