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

Pubmed ID: 26110892

Pubmed Central ID: PMC4482015

Journal: Obesity (Silver Spring, Md.)

Publication Date: July 1, 2015

Affiliation: Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.

MeSH Terms: Humans, Male, Female, Middle Aged, Body Mass Index, Genome-Wide Association Study, Obesity, Waist Circumference, Phenotype, Gene Expression Regulation, DNA Methylation, Epigenesis, Genetic, Carnitine O-Palmitoyltransferase, Epigenomics

Grants: N01 HC025195, N01HC25195, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, T32 HL079888, T32 HL072757, U01 HG004402, R01 HL059367, UL1RR025005, R01HL59367, UL1 RR025005, R01 HL086694, HHSN268200625226C, U01HG004402, R01HL087641, R01 HL087641, R01HL086694, RC2 HL102419, 5RC2HL102419, U01 HL072524, U01HL072524-04, R01 HL104135

Authors: Pankow JS, Guan W, Demerath EW, Lin LA, Boerwinkle E, Fornage M, Grove ML, Ordovas JM, Borecki IB, Arnett DK, Tsai MY, Aslibekyan S, Mendelson M, Irvin MR, Zhi D, Liang L, Liu C, Bressler J, Absher DM, Levy D, Sha J, Hidalgo B, Thibeault KS, Hopkins PN, Tiwari HK

Cite As: Aslibekyan S, Demerath EW, Mendelson M, Zhi D, Guan W, Liang L, Sha J, Pankow JS, Liu C, Irvin MR, Fornage M, Hidalgo B, Lin LA, Thibeault KS, Bressler J, Tsai MY, Grove ML, Hopkins PN, Boerwinkle E, Borecki IB, Ordovas JM, Levy D, Tiwari HK, Absher DM, Arnett DK. Epigenome-wide study identifies novel methylation loci associated with body mass index and waist circumference. Obesity (Silver Spring) 2015 Jul;23(7):1493-501.

Studies:

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.