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Genome-Wide Association Study for Type 2 Diabetes in Indians Identifies a New Susceptibility Locus at 2q21

Diabetes (New York, N.Y.), 2013-03, Vol.62 (3), p.977-986 [Peer Reviewed Journal]

2014 INIST-CNRS ;COPYRIGHT 2013 American Diabetes Association ;COPYRIGHT 2013 American Diabetes Association ;Copyright American Diabetes Association Mar 2013 ;2013 by the American Diabetes Association. 2013 ;ISSN: 0012-1797 ;EISSN: 1939-327X ;DOI: 10.2337/db12-0406 ;PMID: 23209189 ;CODEN: DIAEAZ

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Title:
Genome-Wide Association Study for Type 2 Diabetes in Indians Identifies a New Susceptibility Locus at 2q21
Author: TABASSUM, Rubina ; CHAUHAN, Ganesh ; CHIDAMBARAM, Manickam ; SHARMA, Amitabh ; CHAVALI, Sreenivas ; SENGUPTA, Shantanu ; RAMAKRISHNAN, Lakshmi ; VENKATESH, Pradeep ; AGGARWAL, Sanjay K ; GHOSH, Saurabh ; PRABHAKARAN, Dorairaj ; SRINATH, Reddy K ; OM PRAKASH DWIVEDI ; SAXENA, Madhukar ; BANERJEE, Monisha ; MATHUR, Sandeep ; BHANSALI, Anil ; SHAH, Viral N ; SRI VENKATA MADHU ; MARWAHA, Raman K ; BASU, Analabha ; SCARIA, Vinod ; MCCARTHY, Mark I ; MAHAJAN, Anubha ; VENKATESAN, Radha ; MOHAN, Viswanathan ; TANDON, Nikhil ; BHARADWAJ, Dwaipayan ; JAISWAL, Alok ; KAUR, Ismeet ; BANDESH, Khushdeep ; SINGH, Tejbir ; BENAN JOHN MATHAI ; PANDEY, Yogesh
Subjects: Aged ; Asians ; Biological and medical sciences ; Chromosomes, Human, Pair 2 - genetics ; Demographic aspects ; Diabetes Mellitus, Type 2 - genetics ; Diabetes Mellitus, Type 2 - metabolism ; Diabetes. Impaired glucose tolerance ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Genetic aspects ; Genetic Loci ; Genetic Predisposition to Disease ; Genetics/Genomes/Proteomics/Metabolomics ; Genome-Wide Association Study ; Humans ; India ; Insulin Resistance ; Medical sciences ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Middle Aged ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Polymorphism, Single Nucleotide ; Type 2 diabetes ; Whites
Is Part Of: Diabetes (New York, N.Y.), 2013-03, Vol.62 (3), p.977-986
Description: Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 × 10⁻⁹). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 × 10⁻¹²) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.
Publisher: Alexandria, VA: American Diabetes Association
Language: English
Identifier: ISSN: 0012-1797
EISSN: 1939-327X
DOI: 10.2337/db12-0406
PMID: 23209189
CODEN: DIAEAZ
Source: Open Access: PubMed Central
MEDLINE
Alma/SFX Local Collection
ProQuest Central

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Genome-Wide Association Study for Type 2 Diabetes in Indians Identifies a New Susceptibility Locus at 2q21

2014 INIST-CNRS ;COPYRIGHT 2013 American Diabetes Association ;COPYRIGHT 2013 American Diabetes Association ;Copyright American Diabetes Association Mar 2013 ;2013 by the American Diabetes Association. 2013 ;ISSN: 0012-1797 ;EISSN: 1939-327X ;DOI: 10.2337/db12-0406 ;PMID: 23209189 ;CODEN: DIAEAZ

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