An epigenome-wide study of obesity in African American youth and young adults: novel findings, replication in neutrophils, and relationship with gene expression

Xiaoling Wang, Yue Pan, Haidong Zhu, Guang Hao, Yisong Huang, Vernon Barnes, Huidong Shi, Harold Snieder, James Pankow, Kari North, Megan Grove, Weihua Guan, Ellen Demerath, Yanbin Dong, Shaoyong Su

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: We conducted an epigenome-wide association study (EWAS) on obesity in healthy youth and young adults and further examined to what extent identified signals influenced gene expression and were independent of cell type composition and obesity-related cardio-metabolic risk factors. Genome-wide DNA methylation data from leukocytes were obtained from 700 African Americans aged 14-36. We also measured genome-wide DNA methylation data from neutrophils as well as genome-wide gene expression data from leukocytes in a subset of samples (n = 188). Results: The EWAS identified 76 obesity-related CpG sites in leukocytes with p < 1 × 10-7. In silico replication in the ARIC study of 2097 African Americans aged 47-70 validated 54 CpG sites. Out of the 54 CpG sites, 29 associations with obesity were novel and 37 were replicated in neutrophils. Fifty one CpG sites were associated with at least one cardio-metabolic risk factor; however, the number reduced to 9 after adjustment for obesity. Sixteen CpG sites were associated with expression of 17 genes in cis, of which 5 genes displayed differential expression between obese cases and lean controls. We also replicated 71.5% of obesity-related CpG sites previously reported. Conclusion: In this study of youth and young adults, we identified 29 novel CpG sites associated with obesity and replicated the majority of the CpG sites previously identified. We further demonstrated that the majority of the obesity-related CpG sites in leukocytes were not driven by cell composition or obesity-related cardio-metabolic risk factors. We also provided the direct link between DNA methylation-gene expression-obesity for 5 genes.

Original languageEnglish (US)
Number of pages1
JournalClinical epigenetics
Volume10
DOIs
StatePublished - Jan 1 2018

Fingerprint

African Americans
Young Adult
Neutrophils
Obesity
Gene Expression
Leukocytes
DNA Methylation
Genome
Computer Simulation
Genes

Keywords

  • African Americans
  • DNA methylation
  • Leukocytes
  • Neutrophils
  • Obesity
  • Youth

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Developmental Biology
  • Genetics(clinical)

Cite this

An epigenome-wide study of obesity in African American youth and young adults : novel findings, replication in neutrophils, and relationship with gene expression. / Wang, Xiaoling; Pan, Yue; Zhu, Haidong; Hao, Guang; Huang, Yisong; Barnes, Vernon; Shi, Huidong; Snieder, Harold; Pankow, James; North, Kari; Grove, Megan; Guan, Weihua; Demerath, Ellen; Dong, Yanbin; Su, Shaoyong.

In: Clinical epigenetics, Vol. 10, 01.01.2018.

Research output: Contribution to journalArticle

Wang, Xiaoling ; Pan, Yue ; Zhu, Haidong ; Hao, Guang ; Huang, Yisong ; Barnes, Vernon ; Shi, Huidong ; Snieder, Harold ; Pankow, James ; North, Kari ; Grove, Megan ; Guan, Weihua ; Demerath, Ellen ; Dong, Yanbin ; Su, Shaoyong. / An epigenome-wide study of obesity in African American youth and young adults : novel findings, replication in neutrophils, and relationship with gene expression. In: Clinical epigenetics. 2018 ; Vol. 10.
@article{6da3e3168e41464898a96dea3198c738,
title = "An epigenome-wide study of obesity in African American youth and young adults: novel findings, replication in neutrophils, and relationship with gene expression",
abstract = "Background: We conducted an epigenome-wide association study (EWAS) on obesity in healthy youth and young adults and further examined to what extent identified signals influenced gene expression and were independent of cell type composition and obesity-related cardio-metabolic risk factors. Genome-wide DNA methylation data from leukocytes were obtained from 700 African Americans aged 14-36. We also measured genome-wide DNA methylation data from neutrophils as well as genome-wide gene expression data from leukocytes in a subset of samples (n = 188). Results: The EWAS identified 76 obesity-related CpG sites in leukocytes with p < 1 × 10-7. In silico replication in the ARIC study of 2097 African Americans aged 47-70 validated 54 CpG sites. Out of the 54 CpG sites, 29 associations with obesity were novel and 37 were replicated in neutrophils. Fifty one CpG sites were associated with at least one cardio-metabolic risk factor; however, the number reduced to 9 after adjustment for obesity. Sixteen CpG sites were associated with expression of 17 genes in cis, of which 5 genes displayed differential expression between obese cases and lean controls. We also replicated 71.5{\%} of obesity-related CpG sites previously reported. Conclusion: In this study of youth and young adults, we identified 29 novel CpG sites associated with obesity and replicated the majority of the CpG sites previously identified. We further demonstrated that the majority of the obesity-related CpG sites in leukocytes were not driven by cell composition or obesity-related cardio-metabolic risk factors. We also provided the direct link between DNA methylation-gene expression-obesity for 5 genes.",
keywords = "African Americans, DNA methylation, Leukocytes, Neutrophils, Obesity, Youth",
author = "Xiaoling Wang and Yue Pan and Haidong Zhu and Guang Hao and Yisong Huang and Vernon Barnes and Huidong Shi and Harold Snieder and James Pankow and Kari North and Megan Grove and Weihua Guan and Ellen Demerath and Yanbin Dong and Shaoyong Su",
year = "2018",
month = "1",
day = "1",
doi = "10.1186/s13148-017-0435-2",
language = "English (US)",
volume = "10",
journal = "Clinical Epigenetics",
issn = "1868-7075",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - An epigenome-wide study of obesity in African American youth and young adults

T2 - novel findings, replication in neutrophils, and relationship with gene expression

AU - Wang, Xiaoling

AU - Pan, Yue

AU - Zhu, Haidong

AU - Hao, Guang

AU - Huang, Yisong

AU - Barnes, Vernon

AU - Shi, Huidong

AU - Snieder, Harold

AU - Pankow, James

AU - North, Kari

AU - Grove, Megan

AU - Guan, Weihua

AU - Demerath, Ellen

AU - Dong, Yanbin

AU - Su, Shaoyong

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: We conducted an epigenome-wide association study (EWAS) on obesity in healthy youth and young adults and further examined to what extent identified signals influenced gene expression and were independent of cell type composition and obesity-related cardio-metabolic risk factors. Genome-wide DNA methylation data from leukocytes were obtained from 700 African Americans aged 14-36. We also measured genome-wide DNA methylation data from neutrophils as well as genome-wide gene expression data from leukocytes in a subset of samples (n = 188). Results: The EWAS identified 76 obesity-related CpG sites in leukocytes with p < 1 × 10-7. In silico replication in the ARIC study of 2097 African Americans aged 47-70 validated 54 CpG sites. Out of the 54 CpG sites, 29 associations with obesity were novel and 37 were replicated in neutrophils. Fifty one CpG sites were associated with at least one cardio-metabolic risk factor; however, the number reduced to 9 after adjustment for obesity. Sixteen CpG sites were associated with expression of 17 genes in cis, of which 5 genes displayed differential expression between obese cases and lean controls. We also replicated 71.5% of obesity-related CpG sites previously reported. Conclusion: In this study of youth and young adults, we identified 29 novel CpG sites associated with obesity and replicated the majority of the CpG sites previously identified. We further demonstrated that the majority of the obesity-related CpG sites in leukocytes were not driven by cell composition or obesity-related cardio-metabolic risk factors. We also provided the direct link between DNA methylation-gene expression-obesity for 5 genes.

AB - Background: We conducted an epigenome-wide association study (EWAS) on obesity in healthy youth and young adults and further examined to what extent identified signals influenced gene expression and were independent of cell type composition and obesity-related cardio-metabolic risk factors. Genome-wide DNA methylation data from leukocytes were obtained from 700 African Americans aged 14-36. We also measured genome-wide DNA methylation data from neutrophils as well as genome-wide gene expression data from leukocytes in a subset of samples (n = 188). Results: The EWAS identified 76 obesity-related CpG sites in leukocytes with p < 1 × 10-7. In silico replication in the ARIC study of 2097 African Americans aged 47-70 validated 54 CpG sites. Out of the 54 CpG sites, 29 associations with obesity were novel and 37 were replicated in neutrophils. Fifty one CpG sites were associated with at least one cardio-metabolic risk factor; however, the number reduced to 9 after adjustment for obesity. Sixteen CpG sites were associated with expression of 17 genes in cis, of which 5 genes displayed differential expression between obese cases and lean controls. We also replicated 71.5% of obesity-related CpG sites previously reported. Conclusion: In this study of youth and young adults, we identified 29 novel CpG sites associated with obesity and replicated the majority of the CpG sites previously identified. We further demonstrated that the majority of the obesity-related CpG sites in leukocytes were not driven by cell composition or obesity-related cardio-metabolic risk factors. We also provided the direct link between DNA methylation-gene expression-obesity for 5 genes.

KW - African Americans

KW - DNA methylation

KW - Leukocytes

KW - Neutrophils

KW - Obesity

KW - Youth

UR - http://www.scopus.com/inward/record.url?scp=85056673005&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056673005&partnerID=8YFLogxK

U2 - 10.1186/s13148-017-0435-2

DO - 10.1186/s13148-017-0435-2

M3 - Article

C2 - 29312471

AN - SCOPUS:85056673005

VL - 10

JO - Clinical Epigenetics

JF - Clinical Epigenetics

SN - 1868-7075

ER -