Epigenome-wide association study of plasma lipids in West Africans: the RODAM study
van der Linden, Eva L; Meeks, Karlijn A C; Chilunga, Felix; Hayfron-Benjamin, Charles; Bahendeka, Silver; Klipstein-Grobusch, Kerstin; Venema, Andrea; van den Born, Bert-Jan; Agyemang, Charles; Henneman, Peter; Adeyemo, Adebowale
(2023) EBioMedicine, volume 89
(Article)
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
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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).
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Keywords: Cholesterol, Epigenome-wide association study, Lipids, Methylation, RODAM, Sub-Saharan Africa, West Africa, General Biochemistry,Genetics and Molecular Biology
ISSN: 2352-3964
Publisher: Elsevier
Note: Funding Information: The current work was supported by the European Commission under the Framework Programme (grant number: 278901 ). E.L.L. was supported by a visiting PhD grant from the Fulbright Commission the Netherlands. K.A.C.M. and A.A. are supported by the Intramural Research Program of the National Institutes of Health in the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is supported by the National Human Genome Research Institute , the National Institute of Diabetes and Digestive and Kidney Diseases , the Center for Information Technology , and the Office of the Director at the National Institutes of Health ( 1ZIAHG200362 ). Funding Information: European Commission under the Framework Programme (grant number: 278901).The authors are very grateful to the advisory board members for their valuable support in shaping the methods, to the research assistants, interviewers and other staff of the five research sites, who have taken part in gathering the data and, most of all, to the Ghanaian volunteers participating in this project. We gratefully acknowledge the clinical chemical laboratory from the Academic Medical Centre for their valuable support with standardisation of the laboratory procedures, and the AMC Biobank for support in biobank management and storage of collected samples. The current work was supported by the European Commission under the Framework Programme (grant number: 278901). E.L.L. was supported by a visiting PhD grant from the Fulbright Commission the Netherlands. K.A.C.M. and A.A. are supported by the Intramural Research Program of the National Institutes of Health in the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology, and the Office of the Director at the National Institutes of Health (1ZIAHG200362). Publisher Copyright: © 2023 The Authors
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