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

Rana Dajani, Jin Li, Zhi Wei, Michael E. March, Qianghua Xia, Yousef Khader, Nancy Hakooz, Raja Fatahallah, Mohammed El-Khateeb, Ala Arafat, Tareq Saleh, Abdel Rahman Dajani, Zaid Al-Abbadi, Mohamed Abdul Qader, Abdel Halim Shiyab, Anwar Bateiha, Kamel Ajlouni, Hakon Hakonarson

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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 D1:12×10-8) 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 D4:20×10-5) and it is a robust eQTL for the gene, MLXIP (P D1:10×10-14), 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.

Original languageEnglish (US)
Article numbere3618
JournalPeerJ
Volume2017
Issue number8
DOIs
StatePublished - 2017

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Keywords

  • Genome-wide association study
  • Meta-analysis
  • Methylation
  • Type 2 diabetes
  • eQTL

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