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Epigenome-wide association study (EWAS) of BMI, BMI change and waist circumference in African American adults identifies multiple replicated loci

Human molecular genetics, 2015-08, Vol.24 (15), p.4464-4479 [Peer Reviewed Journal]

The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. ;The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com 2015 ;ISSN: 0964-6906 ;ISSN: 1460-2083 ;EISSN: 1460-2083 ;DOI: 10.1093/hmg/ddv161 ;PMID: 25935004

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Title:
Epigenome-wide association study (EWAS) of BMI, BMI change and waist circumference in African American adults identifies multiple replicated loci
Author: Demerath, Ellen W ; Guan, Weihua ; Grove, Megan L ; Aslibekyan, Stella ; Mendelson, Michael ; Zhou, Yi-Hui ; Hedman, Åsa K ; Sandling, Johanna K ; Li, Li-An ; Irvin, Marguerite R ; Zhi, Degui ; Deloukas, Panos ; Liang, Liming ; Liu, Chunyu ; Bressler, Jan ; Spector, Tim D ; North, Kari ; Li, Yun ; Absher, Devin M ; Levy, Daniel ; Arnett, Donna K ; Fornage, Myriam ; Pankow, James S ; Boerwinkle, Eric
Subjects: African Americans - genetics ; Aged ; Association Studies ; Atherosclerosis - genetics ; Atherosclerosis - pathology ; Body Mass Index ; DNA Methylation - genetics ; Epigenesis, Genetic - genetics ; European Continental Ancestry Group - genetics ; Female ; Genome-Wide Association Study ; Humans ; Lipid Metabolism - genetics ; Male ; Metabolic Networks and Pathways - genetics ; Middle Aged ; Obesity - genetics ; Obesity - pathology ; Waist Circumference - genetics
Is Part Of: Human molecular genetics, 2015-08, Vol.24 (15), p.4464-4479
Description: Obesity is an important component of the pathophysiology of chronic diseases. Identifying epigenetic modifications associated with elevated adiposity, including DNA methylation variation, may point to genomic pathways that are dysregulated in numerous conditions. The Illumina 450K Bead Chip array was used to assay DNA methylation in leukocyte DNA obtained from 2097 African American adults in the Atherosclerosis Risk in Communities (ARIC) study. Mixed-effects regression models were used to test the association of methylation beta value with concurrent body mass index (BMI) and waist circumference (WC), and BMI change, adjusting for batch effects and potential confounders. Replication using whole-blood DNA from 2377 White adults in the Framingham Heart Study and CD4+ T cell DNA from 991 Whites in the Genetics of Lipid Lowering Drugs and Diet Network Study was followed by testing using adipose tissue DNA from 648 women in the Multiple Tissue Human Expression Resource cohort. Seventy-six BMI-related probes, 164 WC-related probes and 8 BMI change-related probes passed the threshold for significance in ARIC (P < 1 × 10(-7); Bonferroni), including probes in the recently reported HIF3A, CPT1A and ABCG1 regions. Replication using blood DNA was achieved for 37 BMI probes and 1 additional WC probe. Sixteen of these also replicated in adipose tissue, including 15 novel methylation findings near genes involved in lipid metabolism, immune response/cytokine signaling and other diverse pathways, including LGALS3BP, KDM2B, PBX1 and BBS2, among others. Adiposity traits are associated with DNA methylation at numerous CpG sites that replicate across studies despite variation in tissue type, ethnicity and analytic approaches.
Publisher: England: Oxford University Press
Language: English
Identifier: ISSN: 0964-6906
ISSN: 1460-2083
EISSN: 1460-2083
DOI: 10.1093/hmg/ddv161
PMID: 25935004
Source: GFMER Free Medical Journals
MEDLINE
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Epigenome-wide association study (EWAS) of BMI, BMI change and waist circumference in African American adults identifies multiple replicated loci

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