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45564

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Principal Investigator: Dharambir Sanghera, PhD, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA MeSH: Diabetes Mellitus, Type 2,Obesity https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000583 The Punjabi Sikh population is a well-defined, carefully collected homogeneous sample from northern India and the US. It has unique characteristics, which are ideal for genetic studies. Sikhs are *strictly* a non-smoking population and about 50% of participants are life-long vegetarians. All subjects included in the genome-wide association studies (GWAS) were recruited from one geographical location. Our population demonstrates a strong familial clustering of type 2 diabetes and related cardio-metabolic disorders that may be genetic and we believe that the contribution of alleles at specific loci are likely to be unique to Punjabi Asians compared to Europeans. Our group first showed that the association of a common variant at rs9939609 in the *FTO* (fat mass and obesity) gene in South Asians was independent of BMI (PMID:18598350) in contrast to Europeans where the association of same variant with T2D is mediated through obesity (PMID:17434869). These findings were later confirmed in an independent sample of South Indians (PMID:19005641), Pakistanis (PMID:21294771), and even East and South Asians in a large meta-analyses study comprising 96,551 individuals (PMID: 22109280). Earlier reported association of *MTNR1B* with fasting glucose concentrations and type 2 diabetes in European GWAS could not be confirmed in our Sikh cohort. On the other hand, our study revealed, for the first time, a significant protective association of another less common variant in *MTNR1B* with fasting glucose levels that was modulated by obesity. Ours was the first report that suggested that the low CETP activity was associated with higher CAD risk (PMID:22143414) in South Asians and that the genetic effects are significantly modulated by environmental factors (alcohol consumption). Our recent GWAS on type 2 diabetes has identified a novel locus at chromosome 13q12 in the *SGCG* gene (p=1.82x10sup-8/sup) associated with type 2 diabetes (PMID:23300278) in Punjabi Sikhs. From these findings, we are optimistic that our resource will provide new insights to gene functions in the diabetic pathway and better help researchers to understand and translate these insights to novel therapeutic treatment and early prevention to T2D that may be important beyond Indians.

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https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000583

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1. 1/13/23 1/13/23 - Nelly Zental

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Dharambir Sanghera, PhD, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

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January 13, 2023

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