A replication study of 49 Type 2 diabetes risk variants in a Punjabi Pakistani population.
The burden of Type 2 diabetes is alarmingly high in South Asia, a region that has many genetically diverse ethnic populations. Genome-wide association studies (GWAS) conducted largely in European populations have identified a number of loci predisposing to Type 2 diabetes risk, however, the relevance of such genetic loci in many South Asian sub-ethnicities remains elusive. The aim of this study was to replicate 49 single nucleotide polymorphisms (SNPs) previously identified through GWAS in Punjabis living in Pakistan.



We examined the association of 49 SNPs in 853 Type 2 diabetes cases and 1945 controls using additive logistic regression models after adjusting for age and gender.



Of the 49 SNPs investigated, eight showed a nominal association (P < 0.05) that also remained significant after controlling for the false discovery rate. The most significant association was found for rs7903146 at the TCF7L2 locus. For a per unit increase in the risk score comprising of all the 49 SNPs, the odds ratio in association with Type 2 diabetes risk was 1.16 (95% CI 1.13-1.19, P < 2.0E-16).



These results suggest that some Type 2 diabetes susceptibility loci are shared between Europeans and Punjabis living in Pakistan.
Atta-Ur-Rahman School of Applied Biosciences (ASAB), National University of Science and Technology (NUST), Islamabad, Pakistan.
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Zia
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, USA.
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Wang
Atta-Ur-Rahman School of Applied Biosciences (ASAB), National University of Science and Technology (NUST), Islamabad, Pakistan.
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Bhatti
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, USA.
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Demirci
Institute of Translational Medicine and Human Genetics, Department of Medicine, University of Pennsylvania, Philadelphia, USA.
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Zhao
Center for Non-Communicable Diseases, Karachi, Pakistan.
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Rasheed
Center for Non-Communicable Diseases, Karachi, Pakistan.
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Samuel
Atta-Ur-Rahman School of Applied Biosciences (ASAB), National University of Science and Technology (NUST), Islamabad, Pakistan.
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Kiani
Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan.
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Ismail
Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan.
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Zafar
Atta-Ur-Rahman School of Applied Biosciences (ASAB), National University of Science and Technology (NUST), Islamabad, Pakistan.
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John
Institute of Translational Medicine and Human Genetics, Department of Medicine, University of Pennsylvania, Philadelphia, USA.|Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, USA.
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Saleheen
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, USA.
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Kamboh
D000328:Adult; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010154:Pakistan; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results