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

Main Article Content

Asif Jan
Fazli Khuda
Rani Akbar


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 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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How to Cite
Jan, A., Zakiullah, Khuda, F. ., & Akbar, R. (2022). Validation of Genome-Wide Association Studies (GWAS)-Identified Type 2 Diabetes Mellitus Risk Variants in Pakistani Pashtun Population. Journal of the ASEAN Federation of Endocrine Societies. Retrieved from
Original Articles
Author Biographies

Asif Jan, University of Peshawar, Pakistan

Department of Pharmacy

Zakiullah, University of Peshawar, Pakistan

Department of Pharmacy

Fazli Khuda, University of Peshawar, Pakistan

Department of Pharmacy

Rani Akbar, Abdul Wali Khan University, Mardan, Pakistan

Department of Pharmacy


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