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

TitleEpigenome-wide study identifies novel methylation loci associated with body mass index and waist circumference.
Publication TypeJournal Article
Year of Publication2015
AuthorsAslibekyan S, Demerath EW, Mendelson M, Zhi D, Guan W, Liang L, Sha J, Pankow JS, Liu C, Irvin MR, Fornage M, Hidalgo B, Lin L-A, Thibeault KStanton, Bressler J, Tsai MY, Grove ML, Hopkins PN, Boerwinkle E, Borecki IB, Ordovas JM, Levy D, Tiwari HK, Absher DM
Secondary AuthorsArnett DK
JournalObesity (Silver Spring)
Volume23
Issue7
Pagination1493-501
Date Published2015 Jul
ISSN1930-739X
KeywordsBody Mass Index, Carnitine O-Palmitoyltransferase, DNA Methylation, Epigenesis, Genetic, Epigenomics, Female, Gene Expression Regulation, Genome-Wide Association Study, Humans, Male, Middle Aged, Obesity, Phenotype, Waist Circumference
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.

DOI10.1002/oby.21111
Alternate JournalObesity (Silver Spring)
PubMed ID26110892
PubMed Central IDPMC4482015
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States
R01 HL104135 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
N01 HC025195 / HC / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
N01HC25195 / HC / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
U01HL072524-04 / HL / NHLBI NIH HHS / United States
T32 HL079888 / HL / NHLBI NIH HHS / United States
5RC2HL102419 / HL / NHLBI NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
U01 HL072524 / HL / NHLBI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
T32 HL072757 / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States