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
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).
