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

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 journal › Article › peer-review

13 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 language	English (US)
Article number	e3618
Journal	PeerJ
Volume	2017
Issue number	8
DOIs	https://doi.org/10.7717/peerj.3618
State	Published - 2017
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Neuroscience
General Biochemistry, Genetics and Molecular Biology
General Agricultural and Biological Sciences

Keywords

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

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10.7717/peerj.3618

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Dajani, R., Li, J., Wei, Z., March, M. E., Xia, Q., Khader, Y., Hakooz, N., Fatahallah, R., El-Khateeb, M., Arafat, A., Saleh, T., Dajani, A. R., Al-Abbadi, Z., Qader, M. A., Shiyab, A. H., Bateiha, A., Ajlouni, K., & Hakonarson, H. (2017). Genome-wide association study identifies novel type II diabetes risk loci in Jordan subpopulations. PeerJ, 2017(8), Article e3618. https://doi.org/10.7717/peerj.3618

@article{b64f7034eaa04a97bb24c8c6081aeec2,

title = "Genome-wide association study identifies novel type II diabetes risk loci in Jordan subpopulations",

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.",

keywords = "Genome-wide association study, Meta-analysis, Methylation, Type 2 diabetes, eQTL",

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

note = "Publisher Copyright: {\textcopyright} 2017 Dajani et al.",

year = "2017",

doi = "10.7717/peerj.3618",

language = "English (US)",

volume = "2017",

journal = "PeerJ",

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Dajani, R, Li, J, Wei, Z, March, ME, Xia, Q, Khader, Y, Hakooz, N, Fatahallah, R, El-Khateeb, M, Arafat, A, Saleh, T, Dajani, AR, Al-Abbadi, Z, Qader, MA, Shiyab, AH, Bateiha, A, Ajlouni, K & Hakonarson, H 2017, 'Genome-wide association study identifies novel type II diabetes risk loci in Jordan subpopulations', PeerJ, vol. 2017, no. 8, e3618. https://doi.org/10.7717/peerj.3618

TY - JOUR

T1 - Genome-wide association study identifies novel type II diabetes risk loci in Jordan subpopulations

AU - Dajani, Rana

AU - Li, Jin

AU - Wei, Zhi

AU - March, Michael E.

AU - Xia, Qianghua

AU - Khader, Yousef

AU - Hakooz, Nancy

AU - Fatahallah, Raja

AU - El-Khateeb, Mohammed

AU - Arafat, Ala

AU - Saleh, Tareq

AU - Dajani, Abdel Rahman

AU - Al-Abbadi, Zaid

AU - Qader, Mohamed Abdul

AU - Shiyab, Abdel Halim

AU - Bateiha, Anwar

AU - Ajlouni, Kamel

AU - Hakonarson, Hakon

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Genome-wide association study

KW - Meta-analysis

KW - Methylation

KW - Type 2 diabetes

KW - eQTL

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DO - 10.7717/peerj.3618

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SN - 2167-8359

VL - 2017

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JF - PeerJ

IS - 8

M1 - e3618

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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