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

doi:10.7717/peerj.3618

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.

Authors

Rana Dajani^#¹, Jin Li^#^{2

3}, Zhi Wei⁴, Michael E March², Qianghua Xia^{3

5}, Yousef Khader⁶, Nancy Hakooz⁷, Raja Fatahallah⁸, Mohammed El-Khateeb⁸, Ala Arafat⁸, Tareq Saleh¹, Abdel Rahman Dajani¹, Zaid Al-Abbadi¹, Mohamed Abdul Qader¹, Abdel Halim Shiyab⁹, Anwar Bateiha⁶, Kamel Ajlouni⁸, Hakon Hakonarson^{2

5

10}

Affiliations

¹ Department of Biology and Biotechnology, Hashemite University, Zarqa, Jordan.
² Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, United States of America.
³ Department of Cell Biology, Tianjin Medical University, Tianjin, China.
⁴ Department of Computer Science, New Jersey Institute of Technology, Newark, NJ, United States of America.
⁵ Divisions of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, United States of America.
⁶ Department of Community Medicine, Public Health and Family Medicine, Faculty of Medicine, Jordan University for Science and Technology, Irbid, Jordan.
⁷ Department of Biopharmaceutics and Clinical Pharmacy, School of Pharmacy, University of Jordan, Amman, Jordan.
⁸ National Center for Diabetes, Endocrinology and Genetics, Amman, Jordan.
⁹ Department of Anthropology, Yarmouk University, Irbid, Jordan.
¹⁰ The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.

^# Contributed equally.

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.

Grants and funding

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.