Epigenome‐wide study identifies novel methylation loci associated with body mass index and waist circumference
Objective To conduct an epigenome‐wide analysis of DNA methylation and obesity traits. Methods DNA methylation was quantified in CD4+ T‐cells using the Illumina Infinium HumanMethylation450 array in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. Methylation at individual...
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| Published in | Obesity (Silver Spring, Md.) Vol. 23; no. 7; pp. 1493 - 1501 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Blackwell Publishing Ltd
01.07.2015
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1930-7381 1930-739X 1930-739X |
| DOI | 10.1002/oby.21111 |
Cover
| Abstract | Objective
To conduct an epigenome‐wide analysis of DNA methylation and obesity traits.
Methods
DNA methylation was quantified in CD4+ T‐cells using the Illumina Infinium HumanMethylation450 array in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. Methylation at individual cytosine‐phosphate‐guanine (CpG) sites as a function of body mass index (BMI) and waist circumference (WC), adjusting for age, gender, study site, T‐cell purity, smoking, and family structure, was modeled.
Results
Epigenome‐wide significant associations between eight CpG sites and BMI and five CpG sites and WC, successfully replicating the top hits in whole blood samples from the Framingham Heart Study (n = 2,377) and the Atherosclerosis Risk in Communities study (n = 2,097), were found. Top findings were in CPT1A (meta‐analysis P = 2.7 × 10−43 for BMI and 9.9 × 10−23 for WC), PHGDH (meta‐analysis P = 2.0 × 10−15 for BMI and 4.0 × 10−9 for WC), CD38 (meta‐analysis P = 6.3 × 10−11 for BMI and 1.6 × 10−12 for WC), and long intergenic non‐coding RNA 00263 (meta‐analysis P = 2.2 × 10−16 for BMI and 8.9 × 10−14 for WC), regions with biologically plausible relationships to adiposity.
Conclusions
This large‐scale epigenome‐wide study discovered and replicated robust associations between DNA methylation at CpG loci and obesity indices, laying the groundwork for future diagnostic and/or therapeutic applications. |
|---|---|
| AbstractList | Objective
To conduct an epigenome‐wide analysis of DNA methylation and obesity traits.
Methods
DNA methylation was quantified in CD4+ T‐cells using the Illumina Infinium HumanMethylation450 array in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. Methylation at individual cytosine‐phosphate‐guanine (CpG) sites as a function of body mass index (BMI) and waist circumference (WC), adjusting for age, gender, study site, T‐cell purity, smoking, and family structure, was modeled.
Results
Epigenome‐wide significant associations between eight CpG sites and BMI and five CpG sites and WC, successfully replicating the top hits in whole blood samples from the Framingham Heart Study (n = 2,377) and the Atherosclerosis Risk in Communities study (n = 2,097), were found. Top findings were in CPT1A (meta‐analysis P = 2.7 × 10−43 for BMI and 9.9 × 10−23 for WC), PHGDH (meta‐analysis P = 2.0 × 10−15 for BMI and 4.0 × 10−9 for WC), CD38 (meta‐analysis P = 6.3 × 10−11 for BMI and 1.6 × 10−12 for WC), and long intergenic non‐coding RNA 00263 (meta‐analysis P = 2.2 × 10−16 for BMI and 8.9 × 10−14 for WC), regions with biologically plausible relationships to adiposity.
Conclusions
This large‐scale epigenome‐wide study discovered and replicated robust associations between DNA methylation at CpG loci and obesity indices, laying the groundwork for future diagnostic and/or therapeutic applications. To conduct an epigenome-wide analysis of DNA methylation and obesity traits.OBJECTIVETo conduct an epigenome-wide analysis of DNA methylation and obesity traits.DNA methylation was quantified in CD4+ T-cells using the Illumina Infinium HumanMethylation450 array in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. Methylation at individual cytosine-phosphate-guanine (CpG) sites as a function of body mass index (BMI) and waist circumference (WC), adjusting for age, gender, study site, T-cell purity, smoking, and family structure, was modeled.METHODSDNA methylation was quantified in CD4+ T-cells using the Illumina Infinium HumanMethylation450 array in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. Methylation at individual cytosine-phosphate-guanine (CpG) sites as a function of body mass index (BMI) and waist circumference (WC), adjusting for age, gender, study site, T-cell purity, smoking, and family structure, was modeled.Epigenome-wide significant associations between eight CpG sites and BMI and five CpG sites and WC, successfully replicating the top hits in whole blood samples from the Framingham Heart Study (n = 2,377) and the Atherosclerosis Risk in Communities study (n = 2,097), were found. Top findings were in CPT1A (meta-analysis P = 2.7 × 10(-43) for BMI and 9.9 × 10(-23) for WC), PHGDH (meta-analysis P = 2.0 × 10(-15) for BMI and 4.0 × 10(-9) for WC), CD38 (meta-analysis P = 6.3 × 10(-11) for BMI and 1.6 × 10(-12) for WC), and long intergenic non-coding RNA 00263 (meta-analysis P = 2.2 × 10(-16) for BMI and 8.9 × 10(-14) for WC), regions with biologically plausible relationships to adiposity.RESULTSEpigenome-wide significant associations between eight CpG sites and BMI and five CpG sites and WC, successfully replicating the top hits in whole blood samples from the Framingham Heart Study (n = 2,377) and the Atherosclerosis Risk in Communities study (n = 2,097), were found. Top findings were in CPT1A (meta-analysis P = 2.7 × 10(-43) for BMI and 9.9 × 10(-23) for WC), PHGDH (meta-analysis P = 2.0 × 10(-15) for BMI and 4.0 × 10(-9) for WC), CD38 (meta-analysis P = 6.3 × 10(-11) for BMI and 1.6 × 10(-12) for WC), and long intergenic non-coding RNA 00263 (meta-analysis P = 2.2 × 10(-16) for BMI and 8.9 × 10(-14) for WC), regions with biologically plausible relationships to adiposity.This large-scale epigenome-wide study discovered and replicated robust associations between DNA methylation at CpG loci and obesity indices, laying the groundwork for future diagnostic and/or therapeutic applications.CONCLUSIONSThis large-scale epigenome-wide study discovered and replicated robust associations between DNA methylation at CpG loci and obesity indices, laying the groundwork for future diagnostic and/or therapeutic applications. To conduct an epigenome-wide analysis of DNA methylation and obesity traits. DNA methylation was quantified in CD4+ T-cells using the Illumina Infinium HumanMethylation450 array in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. Methylation at individual cytosine-phosphate-guanine (CpG) sites as a function of body mass index (BMI) and waist circumference (WC), adjusting for age, gender, study site, T-cell purity, smoking, and family structure, was modeled. Epigenome-wide significant associations between eight CpG sites and BMI and five CpG sites and WC, successfully replicating the top hits in whole blood samples from the Framingham Heart Study (n = 2,377) and the Atherosclerosis Risk in Communities study (n = 2,097), were found. Top findings were in CPT1A (meta-analysis P = 2.7 × 10(-43) for BMI and 9.9 × 10(-23) for WC), PHGDH (meta-analysis P = 2.0 × 10(-15) for BMI and 4.0 × 10(-9) for WC), CD38 (meta-analysis P = 6.3 × 10(-11) for BMI and 1.6 × 10(-12) for WC), and long intergenic non-coding RNA 00263 (meta-analysis P = 2.2 × 10(-16) for BMI and 8.9 × 10(-14) for WC), regions with biologically plausible relationships to adiposity. This large-scale epigenome-wide study discovered and replicated robust associations between DNA methylation at CpG loci and obesity indices, laying the groundwork for future diagnostic and/or therapeutic applications. To conduct an epigenome-wide analysis of DNA methylation and obesity traits. DNA methylation was quantified in CD4+ T-cells using the Illumina Infinium HumanMethylation450 array in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. Methylation at individual cytosine-phosphate-guanine (CpG) sites as a function of body mass index (BMI) and waist circumference (WC), adjusting for age, gender, study site, T-cell purity, smoking, and family structure, was modeled. Epigenome-wide significant associations between eight CpG sites and BMI and five CpG sites and WC, successfully replicating the top hits in whole blood samples from the Framingham Heart Study (n = 2,377) and the Atherosclerosis Risk in Communities study (n = 2,097), were found. Top findings were in CPT1A (meta-analysis P = 2.7 × 10^sup -43^ for BMI and 9.9 × 10^sup -23^ for WC), PHGDH (meta-analysis P = 2.0 × 10^sup -15^ for BMI and 4.0 × 10^sup -9^ for WC), CD38 (meta-analysis P = 6.3 × 10^sup -11^ for BMI and 1.6 × 10^sup -12^ for WC), and long intergenic non-coding RNA 00263 (meta-analysis P = 2.2 × 10^sup -16^ for BMI and 8.9 × 10^sup -14^ for WC), regions with biologically plausible relationships to adiposity. This large-scale epigenome-wide study discovered and replicated robust associations between DNA methylation at CpG loci and obesity indices, laying the groundwork for future diagnostic and/or therapeutic applications. |
| Author | Hopkins, Paul N. Pankow, James S. Aslibekyan, Stella Absher, Devin M. Stanton Thibeault, Krista Boerwinkle, Eric Arnett, Donna K. Fornage, Myriam Mendelson, Michael Grove, Megan L. Zhi, Degui Irvin, Marguerite R. Liang, Liming Sha, Jin Ordovas, Jose M. Liu, Chunyu Bressler, Jan Tiwari, Hemant K. Tsai, Michael Y. Levy, Daniel Demerath, Ellen W. Hidalgo, Bertha Borecki, Ingrid B. Guan, Weihua Lin, Li‐An |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26110892$$D View this record in MEDLINE/PubMed |
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| Copyright | 2015 The Obesity Society 2015 The Obesity Society. Copyright Blackwell Publishing Ltd. Jul 2015 |
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| Notes | The authors declared no conflict of interest. Disclosure Devin M. Absher and Donna K. Arnett are regarded as joint senior authors. Substantial contributions to conception and design: DMA, DKA, SA, EB, JB, EWD, MRI, DL, JMO, HKT; Acquisition of data: DMA, DKA, EB, IBB, JB, EWD, MF, MLG, PNH, DL, JMO, JSP, KST, HKT, MYT; Analysis: DMA, DKA, SA, EWD, WG, LL, LL, CL, MM, JS, KST, DZ; Interpretation of data: DMA, DKA, SA, EWD, WG, BH, LL, LL, CL, MM, JSP, JS, KST, DZ; Drafting of article: SA. All authors were involved in revising the manuscript critically for important intellectual content, and all granted final approval of the submitted and published versions. Author contributions SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 ObjectType-Article-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 The authors wish it to be known that, in their opinion, Devin M. Absher and Donna K. Arnett should be regarded as joint senior authors. |
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| Snippet | Objective
To conduct an epigenome‐wide analysis of DNA methylation and obesity traits.
Methods
DNA methylation was quantified in CD4+ T‐cells using the... To conduct an epigenome-wide analysis of DNA methylation and obesity traits. DNA methylation was quantified in CD4+ T-cells using the Illumina Infinium... To conduct an epigenome-wide analysis of DNA methylation and obesity traits. DNA methylation was quantified in CD4+ T-cells using the Illumina Infinium... To conduct an epigenome-wide analysis of DNA methylation and obesity traits.OBJECTIVETo conduct an epigenome-wide analysis of DNA methylation and obesity... |
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| SubjectTerms | American Recovery & Reinvestment Act 2009-US Body Mass Index Carnitine O-Palmitoyltransferase - genetics Deoxyribonucleic acid DNA DNA methylation DNA Methylation - genetics Epigenesis, Genetic - genetics Epigenetics Epigenomics - methods Female Gene expression Gene Expression Regulation - physiology Genetic testing Genome-Wide Association Study - methods Genomes Heart Humans Lipids Male Methods Middle Aged Obesity Obesity - genetics Phenotype Quality control Software Studies Waist Circumference - genetics |
| Title | Epigenome‐wide study identifies novel methylation loci associated with body mass index and waist circumference |
| URI | https://onlinelibrary.wiley.com/doi/abs/10.1002%2Foby.21111 https://www.ncbi.nlm.nih.gov/pubmed/26110892 https://www.proquest.com/docview/1702909732 https://www.proquest.com/docview/1691598465 https://pubmed.ncbi.nlm.nih.gov/PMC4482015 |
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