Associations between epigenome-wide DNA methylation and height-related traits among Sub-Saharan Africans: the RODAM study.

Abstract

Human height and related traits are highly complex, and extensively research has shown that these traits are determined by both genetic and environmental factors. Such factors may partially affect these traits through epigenetic programing. Epigenetic programing is dynamic and plays an important role in controlling gene expression and cell differentiation during (early) development. DNA methylation (DNAm) is the most commonly studied epigenetic feature. In this study we conducted an epigenome-wide DNAm association analysis on height-related traits in a Sub-Saharan African population, in order to detect DNAm biomarkers across four height-related traits. DNAm profiles were acquired in whole blood samples of 704 Ghanaians, sourced from the Research on Obesity and Diabetes among African Migrants study, using the Illumina Infinium HumanMethylation450 BeadChip. Linear models were fitted to detect differentially methylated positions (DMPs) and regions (DMRs) associated with height, leg-to-height ratio (LHR), leg length, and sitting height. No epigenome-wide significant DMPs were recorded. However we did observe among our top DMPs five informative probes associated with the height-related traits: cg26905768 (leg length), cg13268132 (leg length), cg19776793 (height), cg23072383 (LHR), and cg24625894 (sitting height). All five DMPs are annotated to genes whose functions were linked to bone cell regulation and development. DMR analysis identified overlapping DMRs within the gene body of HLA-DPB1 gene, and the HOXA gene cluster. In this first epigenome-wide association studies of these traits, our findings suggest DNAm associations with height-related heights, and might influence development and maintenance of these traits. Further studies are needed to replicate our findings, and to elucidate the molecular mechanism underlying human height-related traits.