Validation of Genome-Wide Association Studies (GWAS)-Identified Type 2 Diabetes Mellitus Risk Variants in Pakistani Pashtun Population

Asif Jan; Zakiullah; Fazli  Khuda; Rani  Akbar

doi:10.15605/jafes.037.S5

Authors

Asif Jan University of Peshawar, Pakistan https://orcid.org/0000-0003-3880-5579
Zakiullah University of Peshawar, Pakistan https://orcid.org/0000-0001-7932-9498
Fazli Khuda University of Peshawar
Rani Akbar Abdul Wali Khan University, Mardan, Pakistan

DOI:

https://doi.org/10.15605/jafes.037.S5

Keywords:

Type 2 Diabetes Mellitus, European GWAS, SNPs validation, replication study, Pashtun population

Abstract

Objective. Recent GWAS largely conducted in European populations have successfully identified multiple genetic risk variants associated with Type 2 Diabetes Mellitus (T2DM). However, the effects conferred by these variants in the Pakistani population have not yet been fully elucidated. The objective of this study was to examine European GWAS- identified T2DM risk variants in the Pakistani Pashtun population to better understand the shared genetic basis of T2DM in the European and Pakistani cohorts.

Methodology. A total of 100 T2DM patients and 100 healthy volunteers of Pashtun ethnicity were enrolled in this study. Both groups were genotyped for 8 selected single nucleotide polymorphisms (SNPs) using the Sequenom MassARRAY® platform. The association between selected SNPs and T2DM was determined by using appropriate statistical tests.

Results. Of the 8 studied SNPs, 5 SNPs, SLC30A8/ rs13266634 (p=0.031, OR=2.13), IGF2BP2/ rs4402960 (p=0.001, OR=3.01), KCNJ11/ rs5219 (p=0.042, OR=1.78), PPARG/ rs1801282 (p=0.042, OR=2.81) and TCF7L2/ rs7903146 (p=0.00006, 3.41) had a significant association with T2DM. SNP GLIS3/ rs7041847 (p=0.051, OR=2.01) showed no sufficient evidence of association. SNPs KCNQ1/ rs2237892 (p=0.140, OR=1.61) and HHEX/IDE/ s1111875 (p=0.112, OR=1.31) showed opposite allelic effects and were not validated for T2DM risk in the study population. Among the studied SNPs, TCF7L2/ rs7903146 showed the most significant association.

Conclusion. Our study finding indicates that selected genome-wide significant T2DM risk variants previously identified
in European descent also increase the risk of developing T2DM in the Pakistani Pashtun population.

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Author Biographies

Asif Jan, University of Peshawar, Pakistan

Research Associate (Genomics), Department of Pharmacy

Zakiullah, University of Peshawar, Pakistan

Assistant Professor, Department of Pharmacy

Fazli Khuda, University of Peshawar

Assistant Professor, Department of Pharmacy

Rani Akbar, Abdul Wali Khan University, Mardan, Pakistan

MPhil Research Scholar, Department of Pharmacy

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