Genome-wide association study identifies novel type II diabetes risk loci in Jordan subpopulations

PeerJ. 2017 Aug 17;5:e3618. doi: 10.7717/peerj.3618. eCollection 2017.

Abstract

The prevalence of Type II Diabetes (T2D) has been increasing and has become a disease of significant public health burden in Jordan. None of the previous genome-wide association studies (GWAS) have specifically investigated the Middle East populations. The Circassian and Chechen communities in Jordan represent unique populations that are genetically distinct from the Arab population and other populations in the Caucasus. Prevalence of T2D is very high in both the Circassian and Chechen communities in Jordan despite low obesity prevalence. We conducted GWAS on T2D in these two populations and further performed meta-analysis of the results. We identified a novel T2D locus at chr20p12.2 at genome-wide significance (rs6134031, P = 1.12 × 10-8) and we replicated the results in the Wellcome Trust Case Control Consortium (WTCCC) dataset. Another locus at chr12q24.31 is associated with T2D at suggestive significance level (top SNP rs4758690, P = 4.20 × 10-5) and it is a robust eQTL for the gene, MLXIP (P = 1.10 × 10-14), and is significantly associated with methylation level in MLXIP, the functions of which involves cellular glucose response. Therefore, in this first GWAS of T2D in Jordan subpopulations, we identified novel and unique susceptibility loci which may help inform the genetic underpinnings of T2D in other populations.

Keywords: Genome-wide association study; Meta-analysis; Methylation; Type 2 diabetes; eQTL.

Grant support

This work was supported by the King Hussein Center for Cancer and Biotechnology and the Higher Council for Science and Technology, Amman, Jordan, and by an Institutional Development Award from The Children’s Hospital of Philadelphia to the Center for Applied Genomics. There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.