Genome-wide analysis yields new loci associating with aortic valve stenosis

Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of Euro...

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Published inNature communications Vol. 9; no. 1; pp. 987 - 10
Main Authors Helgadottir, Anna, Thorleifsson, Gudmar, Gretarsdottir, Solveig, Stefansson, Olafur A., Tragante, Vinicius, Thorolfsdottir, Rosa B., Jonsdottir, Ingileif, Bjornsson, Thorsteinn, Steinthorsdottir, Valgerdur, Verweij, Niek, Nielsen, Jonas B., Zhou, Wei, Folkersen, Lasse, Martinsson, Andreas, Heydarpour, Mahyar, Prakash, Siddharth, Oskarsson, Gylfi, Gudbjartsson, Tomas, Geirsson, Arnar, Olafsson, Isleifur, Sigurdsson, Emil L., Almgren, Peter, Melander, Olle, Franco-Cereceda, Anders, Hamsten, Anders, Fritsche, Lars, Lin, Maoxuan, Yang, Bo, Hornsby, Whitney, Guo, Dongchuan, Brummett, Chad M., Abecasis, Gonçalo, Mathis, Michael, Milewicz, Dianna, Body, Simon C., Eriksson, Per, Willer, Cristen J., Hveem, Kristian, Newton-Cheh, Christopher, Smith, J. Gustav, Danielsen, Ragnar, Thorgeirsson, Gudmundur, Thorsteinsdottir, Unnur, Gudbjartsson, Daniel F., Holm, Hilma, Stefansson, Kari
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 07.03.2018
Nature Publishing Group
Nature Portfolio
Subjects
38/77
45/23
45/43
631/208/205/2138
692/4019/592/2726
692/4019/592/75/1539
692/4019/592/75/591
Abnormalities
Aortic valve
Aortic Valve Stenosis - genetics
Arteriosclerosis
Atherosclerosis
Basic Medicine
Cardiology and Cardiovascular Disease
Cardiovascular disease
Cardiovascular diseases
Case-Control Studies
Cholesterol
Chromosome 1
Chromosome 2
Clinical Medicine
Coronary artery
Coronary artery disease
Coronary Artery Disease - genetics
Genome-Wide Association Study
Genomes
Heart
Heart diseases
Humanities and Social Sciences
Humans
Kardiologi och kardiovaskulära sjukdomar
Klinisk medicin
Loci
Low density lipoprotein
Medical and Health Sciences
Medical Genetics and Genomics (including Gene Therapy)
Medicin och hälsovetenskap
Medicinsk genetik och genomik (Här ingår: Genterapi)
Medicinska och farmaceutiska grundvetenskaper
multidisciplinary
Pathogenesis
Phenotype
Rheumatic heart disease
Risk analysis
Risk Factors
Risk sharing
Science
Science (multidisciplinary)
Stenosis
Online AccessGet full text
ISSN2041-1723
2041-1723
DOI10.1038/s41467-018-03252-6

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Abstract Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR) = 1.20, P  = 1.2 × 10 −22 ) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P  = 1.8 × 10 −13 ). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P  = 6.6 × 10 −10 ) and aortic root diameter ( P  = 1.30 × 10 −8 ), and rs1830321 associates with BAV (OR = 1.12, P  = 5.3 × 10 −3 ) and coronary artery disease (OR = 1.05, P  = 9.3 × 10 −5 ). The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. We show that several pathways are shared by CAD and AS. Causal analysis suggests that the shared risk factors of Lp(a) and non-high-density lipoprotein cholesterol contribute substantially to the frequent co-occurence of these diseases. Aortic valve stenosis (AS) is the most common valvular heart disease. Here the authors identify two new AS loci that also associate with bicuspid aortic valve, aortic root diameter and/or coronary artery disease implicating both developmental abnormalities and atherosclerosis-like processes in AS.
AbstractList Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR) = 1.20, P  = 1.2 × 10 −22 ) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P  = 1.8 × 10 −13 ). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P  = 6.6 × 10 −10 ) and aortic root diameter ( P  = 1.30 × 10 −8 ), and rs1830321 associates with BAV (OR = 1.12, P  = 5.3 × 10 −3 ) and coronary artery disease (OR = 1.05, P  = 9.3 × 10 −5 ). The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. We show that several pathways are shared by CAD and AS. Causal analysis suggests that the shared risk factors of Lp(a) and non-high-density lipoprotein cholesterol contribute substantially to the frequent co-occurence of these diseases. Aortic valve stenosis (AS) is the most common valvular heart disease. Here the authors identify two new AS loci that also associate with bicuspid aortic valve, aortic root diameter and/or coronary artery disease implicating both developmental abnormalities and atherosclerosis-like processes in AS.
Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR) = 1.20, P  = 1.2 × 10 −22 ) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P  = 1.8 × 10 −13 ). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P  = 6.6 × 10 −10 ) and aortic root diameter ( P  = 1.30 × 10 −8 ), and rs1830321 associates with BAV (OR = 1.12, P  = 5.3 × 10 −3 ) and coronary artery disease (OR = 1.05, P  = 9.3 × 10 −5 ). The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. We show that several pathways are shared by CAD and AS. Causal analysis suggests that the shared risk factors of Lp(a) and non-high-density lipoprotein cholesterol contribute substantially to the frequent co-occurence of these diseases.
Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR) = 1.20, P = 1.2 × 10 ) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P = 1.8 × 10 ). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P = 6.6 × 10 ) and aortic root diameter (P = 1.30 × 10 ), and rs1830321 associates with BAV (OR = 1.12, P = 5.3 × 10 ) and coronary artery disease (OR = 1.05, P = 9.3 × 10 ). The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. We show that several pathways are shared by CAD and AS. Causal analysis suggests that the shared risk factors of Lp(a) and non-high-density lipoprotein cholesterol contribute substantially to the frequent co-occurence of these diseases.
Aortic valve stenosis (AS) is the most common valvular heart disease. Here the authors identify two new AS loci that also associate with bicuspid aortic valve, aortic root diameter and/or coronary artery disease implicating both developmental abnormalities and atherosclerosis-like processes in AS.
Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR) = 1.20, P = 1.2 × 10-22) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P = 1.8 × 10-13). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P = 6.6 × 10-10) and aortic root diameter (P = 1.30 × 10-8), and rs1830321 associates with BAV (OR = 1.12, P = 5.3 × 10-3) and coronary artery disease (OR = 1.05, P = 9.3 × 10-5). The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. We show that several pathways are shared by CAD and AS. Causal analysis suggests that the shared risk factors of Lp(a) and non-high-density lipoprotein cholesterol contribute substantially to the frequent co-occurence of these diseases.Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR) = 1.20, P = 1.2 × 10-22) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P = 1.8 × 10-13). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P = 6.6 × 10-10) and aortic root diameter (P = 1.30 × 10-8), and rs1830321 associates with BAV (OR = 1.12, P = 5.3 × 10-3) and coronary artery disease (OR = 1.05, P = 9.3 × 10-5). The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. We show that several pathways are shared by CAD and AS. Causal analysis suggests that the shared risk factors of Lp(a) and non-high-density lipoprotein cholesterol contribute substantially to the frequent co-occurence of these diseases.
Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR) = 1.20, P = 1.2 × 10−22) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P = 1.8 × 10−13). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P = 6.6 × 10−10) and aortic root diameter (P = 1.30 × 10−8), and rs1830321 associates with BAV (OR = 1.12, P = 5.3 × 10−3) and coronary artery disease (OR = 1.05, P = 9.3 × 10−5). The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. We show that several pathways are shared by CAD and AS. Causal analysis suggests that the shared risk factors of Lp(a) and non-high-density lipoprotein cholesterol contribute substantially to the frequent co-occurence of these diseases.
Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR) = 1.20, P = 1.2 × 10-22) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P = 1.8 × 10-13). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P = 6.6 × 10-10) and aortic root diameter (P = 1.30 × 10-8), and rs1830321 associates with BAV (OR = 1.12, P = 5.3 × 10-3) and coronary artery disease (OR = 1.05, P = 9.3 × 10-5). The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. We show that several pathways are shared by CAD and AS. Causal analysis suggests that the shared risk factors of Lp(a) and non-high-density lipoprotein cholesterol contribute substantially to the frequent co-occurence of these diseases.
ArticleNumber 987
Author Brummett, Chad M.
Thorleifsson, Gudmar
Folkersen, Lasse
Abecasis, Gonçalo
Geirsson, Arnar
Thorgeirsson, Gudmundur
Helgadottir, Anna
Milewicz, Dianna
Guo, Dongchuan
Oskarsson, Gylfi
Hornsby, Whitney
Danielsen, Ragnar
Eriksson, Per
Thorsteinsdottir, Unnur
Fritsche, Lars
Willer, Cristen J.
Steinthorsdottir, Valgerdur
Almgren, Peter
Olafsson, Isleifur
Mathis, Michael
Nielsen, Jonas B.
Hveem, Kristian
Newton-Cheh, Christopher
Holm, Hilma
Melander, Olle
Bjornsson, Thorsteinn
Franco-Cereceda, Anders
Gudbjartsson, Daniel F.
Tragante, Vinicius
Smith, J. Gustav
Verweij, Niek
Stefansson, Kari
Thorolfsdottir, Rosa B.
Jonsdottir, Ingileif
Zhou, Wei
Body, Simon C.
Gudbjartsson, Tomas
Prakash, Siddharth
Sigurdsson, Emil L.
Heydarpour, Mahyar
Martinsson, Andreas
Yang, Bo
Gretarsdottir, Solveig
Hamsten, Anders
Stefansson, Olafur A.
Lin, Maoxuan
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/29511194$$D View this record in MEDLINE/PubMed
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Copyright The Author(s) 2018
2018. This work is published 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.
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  publication-title: N. Engl. J. Med.
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Snippet Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large...
Aortic valve stenosis (AS) is the most common valvular heart disease. Here the authors identify two new AS loci that also associate with bicuspid aortic valve,...
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SubjectTerms 38/77
45/23
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692/4019/592/2726
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692/4019/592/75/591
Abnormalities
Aortic valve
Aortic Valve Stenosis - genetics
Arteriosclerosis
Atherosclerosis
Basic Medicine
Cardiology and Cardiovascular Disease
Cardiovascular disease
Cardiovascular diseases
Case-Control Studies
Cholesterol
Chromosome 1
Chromosome 2
Clinical Medicine
Coronary artery
Coronary artery disease
Coronary Artery Disease - genetics
Genome-Wide Association Study
Genomes
Heart
Heart diseases
Humanities and Social Sciences
Humans
Kardiologi och kardiovaskulära sjukdomar
Klinisk medicin
Loci
Low density lipoprotein
Medical and Health Sciences
Medical Genetics and Genomics (including Gene Therapy)
Medicin och hälsovetenskap
Medicinsk genetik och genomik (Här ingår: Genterapi)
Medicinska och farmaceutiska grundvetenskaper
multidisciplinary
Pathogenesis
Phenotype
Rheumatic heart disease
Risk analysis
Risk Factors
Risk sharing
Science
Science (multidisciplinary)
Stenosis
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Title Genome-wide analysis yields new loci associating with aortic valve stenosis
URI https://link.springer.com/article/10.1038/s41467-018-03252-6
https://www.ncbi.nlm.nih.gov/pubmed/29511194
https://www.proquest.com/docview/2011301588
https://www.proquest.com/docview/2011616583
https://pubmed.ncbi.nlm.nih.gov/PMC5840367
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