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

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

doi:10.1016/j.ebiom.2023.104469

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

EBioMedicine. 2023 Mar:89:104469. doi: 10.1016/j.ebiom.2023.104469. Epub 2023 Feb 13.

Affiliations

¹ 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. Electronic address: e.l.vanderlinden@amsterdamumc.nl.
² 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.
³ Department of Public and Occupational Health, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
⁴ Department of Physiology, University of Ghana Medical School, Accra, Ghana; Department of Anesthesia and Critical Care, Korle Bu Teaching Hospital, Accra, Ghana.
⁵ MKPGMS-Uganda Martyrs University, Kampala, Uganda.
⁶ 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.
⁷ Department of Human Genetics, Genome Diagnostics Laboratory Amsterdam, Reproduction & Development, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
⁸ 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.
⁹ Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.

Abstract

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).

Keywords: Cholesterol; Epigenome-wide association study; Lipids; Methylation; RODAM; Sub-Saharan Africa; West Africa.

MeSH terms

African People
Cholesterol
DNA Methylation
Epigenesis, Genetic*
Epigenome*
Genome-Wide Association Study
Ghana
Humans
Lipids* / blood
Longitudinal Studies
Triglycerides

Substances

Cholesterol
Triglycerides
Lipids