Epigenome-wide association study of plasma lipids in West Africans: the RODAM studyResearch in context

Eva L. van der Linden; Karlijn A.C. Meeks; Felix Chilunga; Charles Hayfron-Benjamin; Silver Bahendeka; Kerstin Klipstein-Grobusch; Andrea Venema; Bert-Jan van den Born; Charles Agyemang; Peter Henneman; Adebowale Adeyemo

EBioMedicine (Mar 2023)

Epigenome-wide association study of plasma lipids in West Africans: the RODAM studyResearch in context

Eva L. van der Linden,
Karlijn A.C. Meeks,
Felix Chilunga,
Charles Hayfron-Benjamin,
Silver Bahendeka,
Kerstin Klipstein-Grobusch,
Andrea Venema,
Bert-Jan van den Born,
Charles Agyemang,
Peter Henneman,
Adebowale Adeyemo

Affiliations

Eva L. van der Linden: Department of Public and Occupational Health, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands; Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands; Corresponding author. Department of Public & Occupational Health, Amsterdam UMC, Location VUmc, Post box 7057, 1007 MB Amsterdam, the Netherlands.
Karlijn A.C. Meeks: Department of Public and Occupational Health, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Felix Chilunga: Department of Public and Occupational Health, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
Charles Hayfron-Benjamin: Department of Physiology, University of Ghana Medical School, Accra, Ghana; Department of Anesthesia and Critical Care, Korle Bu Teaching Hospital, Accra, Ghana
Silver Bahendeka: MKPGMS-Uganda Martyrs University, Kampala, Uganda
Kerstin Klipstein-Grobusch: Julius Global Health, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, the Netherlands; Division of Epidemiology and Biostatistics, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
Andrea Venema: Department of Human Genetics, Genome Diagnostics Laboratory Amsterdam, Reproduction & Development, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Bert-Jan van den Born: Department of Public and Occupational Health, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands; Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
Charles Agyemang: Department of Public and Occupational Health, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
Peter Henneman: Department of Human Genetics, Genome Diagnostics Laboratory Amsterdam, Reproduction & Development, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Adebowale Adeyemo: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA

Journal volume & issue: Vol. 89
p. 104469

Abstract

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Summary: Background: DNA-methylation has been associated with plasma lipid concentration in populations of diverse ethnic backgrounds, but epigenome-wide association studies (EWAS) in West-Africans are lacking. The aim of this study was to identify DNA-methylation loci associated with plasma lipids in Ghanaians. Methods: We conducted an EWAS using Illumina 450k DNA-methylation array profiles of extracted DNA from 663 Ghanaian participants. Differentially methylated positions (DMPs) were examined for association with plasma total cholesterol (TC), LDL-cholesterol, HDL-cholesterol, and triglycerides concentrations using linear regression models adjusted for age, sex, body mass index, diabetes mellitus, and technical covariates. Findings were replicated in independent cohorts of different ethnicities. Findings: We identified one significantly associated DMP with triglycerides (cg19693031 annotated to TXNIP, regression coefficient beta −0.26, false discovery rate adjusted p-value 0.001), which replicated in-silico in South African Batswana, African American, and European populations. From the top five DMPs with the lowest nominal p-values, two additional DMPs for triglycerides (CPT1A, ABCG1), two DMPs for LDL-cholesterol (EPSTI1, cg13781819), and one for TC (TXNIP) replicated. With the exception of EPSTI1, these loci are involved in lipid transport/metabolism or are known GWAS-associated loci. The top 5 DMPs per lipid trait explained 9.5% in the variance of TC, 8.3% in LDL-cholesterol, 6.1% in HDL-cholesterol, and 11.0% in triglycerides. Interpretation: The top DMPs identified in this study are in loci that play a role in lipid metabolism across populations, including West-Africans. Future studies including larger sample size, longitudinal study design and translational research is needed to increase our understanding on the epigenetic regulation of lipid metabolism among West-African populations. Funding: European Commission under the Framework Programme (grant number: 278901).

Published in EBioMedicine

ISSN: 2352-3964 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General)
Website: http://www.journals.elsevier.com/ebiomedicine/

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