Epigenome-wide study identifies novel methylation loci associated with body mass index and waist circumference

被引：136

作者：

Aslibekyan, Stella ^{[1
]}

Demerath, Ellen W. ^{[2
]}

Mendelson, Michael ^{[3
,4
,5
]}

Zhi, Degui ^{[6
]}

Guan, Weihua ^{[7
]}

Liang, Liming ^{[3
,4
,8
,9
]}

Sha, Jin ^{[1
]}

Pankow, James S. ^{[2
]}

Liu, Chunyu ^{[4
,10
]}

Irvin, Marguerite R. ^{[1
]}

Fornage, Myriam ^{[11
,12
]}

Hidalgo, Bertha ^{[1
]}

Lin, Li-An ^{[12
]}

Stanton Thibeault, Krista ^{[13
]}

Bressler, Jan ^{[12
]}

Tsai, Michael Y. ^{[14
]}

Grove, Megan L. ^{[12
]}

Hopkins, Paul N. ^{[15
]}

Boerwinkle, Eric ^{[11
,12
]}

Borecki, Ingrid B. ^{[16
]}

Ordovas, Jose M. ^{[17
,18
,19
]}

Levy, Daniel ^{[3
,4
]}

Tiwari, Hemant K. ^{[6
]}

Absher, Devin M. ^{[13
]}

Arnett, Donna K. ^{[1
]}

机构：

[1] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA

[2] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA

[3] NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA

[4] Framingham Heart Dis Epidemiol Study, Framingham, MA USA

[5] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA

[6] Univ Alabama Birmingham, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA

[7] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN USA

[8] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[9] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[10] Boston Univ, Dept Biostat, Boston, MA 02215 USA

[11] Univ Texas Hlth Sci Ctr Houston, Brown Fdn, Inst Mol Med, Houston, TX 77030 USA

[12] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA

[13] HudsonAlpha Inst Biotechnol, Huntsville, AL USA

[14] Univ Minnesota, Div Lab Med & Pathol, Minneapolis, MN USA

[15] Univ Utah, Sch Med, Salt Lake City, UT USA

[16] Washington Univ, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA

[17] Ctr Nacl Invest Cardiovasc, Dept Epidemiol Atherothrombosis & Imaging, Madrid, Spain

[18] Inst Madrileno Estudios Avanzados Alimentac, Madrid, Spain

[19] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA

来源：

OBESITY | 2015年 / 23卷 / 07期

基金：

美国国家卫生研究院;

关键词：

MONOUNSATURATED FATTY-ACIDS; LIPID-LOWERING DRUGS; DNA METHYLATION; OBESITY; GENE; EXPRESSION; PATTERNS; POLYMORPHISMS; EPIGENETICS; ACTIVATION;

D O I：

10.1002/oby.21111

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

ObjectiveTo conduct an epigenome-wide analysis of DNA methylation and obesity traits. 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. 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 x 10(-43) for BMI and 9.9 x 10(-23) for WC), PHGDH (meta-analysis P=2.0 x 10(-15) for BMI and 4.0 x 10(-9) for WC), CD38 (meta-analysis P=6.3 x 10(-11) for BMI and 1.6 x 10(-12) for WC), and long intergenic non-coding RNA 00263 (meta-analysis P=2.2 x 10(-16) for BMI and 8.9 x 10(-14) for WC), regions with biologically plausible relationships to adiposity. 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.

引用

页码：1493 / 1501

页数：9

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