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

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 Jorda...

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Autores principales: Dajani, Rana, Li, Jin, Wei, Zhi, March, Michael E., Xia, Qianghua, Khader, Yousef, Hakooz, Nancy, Fatahallah, Raja, El-Khateeb, Mohammed, Arafat, Ala, Saleh, Tareq, Dajani, Abdel Rahman, Al-Abbadi, Zaid, Abdul Qader, Mohamed, Shiyab, Abdel Halim, Bateiha, Anwar, Ajlouni, Kamel, Hakonarson, Hakon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5563445/
https://www.ncbi.nlm.nih.gov/pubmed/28828242
http://dx.doi.org/10.7717/peerj.3618
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author Dajani, Rana
Li, Jin
Wei, Zhi
March, Michael E.
Xia, Qianghua
Khader, Yousef
Hakooz, Nancy
Fatahallah, Raja
El-Khateeb, Mohammed
Arafat, Ala
Saleh, Tareq
Dajani, Abdel Rahman
Al-Abbadi, Zaid
Abdul Qader, Mohamed
Shiyab, Abdel Halim
Bateiha, Anwar
Ajlouni, Kamel
Hakonarson, Hakon
author_facet Dajani, Rana
Li, Jin
Wei, Zhi
March, Michael E.
Xia, Qianghua
Khader, Yousef
Hakooz, Nancy
Fatahallah, Raja
El-Khateeb, Mohammed
Arafat, Ala
Saleh, Tareq
Dajani, Abdel Rahman
Al-Abbadi, Zaid
Abdul Qader, Mohamed
Shiyab, Abdel Halim
Bateiha, Anwar
Ajlouni, Kamel
Hakonarson, Hakon
author_sort Dajani, Rana
collection PubMed
description 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.
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spelling pubmed-55634452017-08-21 Genome-wide association study identifies novel type II diabetes risk loci in Jordan subpopulations Dajani, Rana Li, Jin Wei, Zhi March, Michael E. Xia, Qianghua Khader, Yousef Hakooz, Nancy Fatahallah, Raja El-Khateeb, Mohammed Arafat, Ala Saleh, Tareq Dajani, Abdel Rahman Al-Abbadi, Zaid Abdul Qader, Mohamed Shiyab, Abdel Halim Bateiha, Anwar Ajlouni, Kamel Hakonarson, Hakon PeerJ Genetics 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. PeerJ Inc. 2017-08-17 /pmc/articles/PMC5563445/ /pubmed/28828242 http://dx.doi.org/10.7717/peerj.3618 Text en ©2017 Dajani et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Genetics
Dajani, Rana
Li, Jin
Wei, Zhi
March, Michael E.
Xia, Qianghua
Khader, Yousef
Hakooz, Nancy
Fatahallah, Raja
El-Khateeb, Mohammed
Arafat, Ala
Saleh, Tareq
Dajani, Abdel Rahman
Al-Abbadi, Zaid
Abdul Qader, Mohamed
Shiyab, Abdel Halim
Bateiha, Anwar
Ajlouni, Kamel
Hakonarson, Hakon
Genome-wide association study identifies novel type II diabetes risk loci in Jordan subpopulations
title Genome-wide association study identifies novel type II diabetes risk loci in Jordan subpopulations
title_full Genome-wide association study identifies novel type II diabetes risk loci in Jordan subpopulations
title_fullStr Genome-wide association study identifies novel type II diabetes risk loci in Jordan subpopulations
title_full_unstemmed Genome-wide association study identifies novel type II diabetes risk loci in Jordan subpopulations
title_short Genome-wide association study identifies novel type II diabetes risk loci in Jordan subpopulations
title_sort genome-wide association study identifies novel type ii diabetes risk loci in jordan subpopulations
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5563445/
https://www.ncbi.nlm.nih.gov/pubmed/28828242
http://dx.doi.org/10.7717/peerj.3618
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