title: Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.
abstract: 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.
authors.affiliation: Genomics and Molecular Medicine Unit, Council for Scientific and Industrial Research-Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Rubina
authors.initials: R
authors.lastname: Tabassum
authors.forename: Ganesh
authors.initials: G
authors.lastname: Chauhan
authors.forename: Om Prakash
authors.initials: OP
authors.lastname: Dwivedi
authors.forename: Anubha
authors.initials: A
authors.lastname: Mahajan
authors.forename: Alok
authors.initials: A
authors.lastname: Jaiswal
authors.forename: Ismeet
authors.initials: I
authors.lastname: Kaur
authors.forename: Khushdeep
authors.initials: K
authors.lastname: Bandesh
authors.forename: Tejbir
authors.initials: T
authors.lastname: Singh
authors.forename: Benan John
authors.initials: BJ
authors.lastname: Mathai
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Pandey
authors.forename: Manickam
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authors.lastname: Chidambaram
authors.forename: Amitabh
authors.initials: A
authors.lastname: Sharma
authors.forename: Sreenivas
authors.initials: S
authors.lastname: Chavali
authors.forename: Shantanu
authors.initials: S
authors.lastname: Sengupta
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Ramakrishnan
authors.forename: Pradeep
authors.initials: P
authors.lastname: Venkatesh
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Aggarwal
authors.forename: Saurabh
authors.initials: S
authors.lastname: Ghosh
authors.forename: Dorairaj
authors.initials: D
authors.lastname: Prabhakaran
authors.forename: Reddy K
authors.initials: RK
authors.lastname: Srinath
authors.forename: Madhukar
authors.initials: M
authors.lastname: Saxena
authors.forename: Monisha
authors.initials: M
authors.lastname: Banerjee
authors.forename: Sandeep
authors.initials: S
authors.lastname: Mathur
authors.forename: Anil
authors.initials: A
authors.lastname: Bhansali
authors.forename: Viral N
authors.initials: VN
authors.lastname: Shah
authors.forename: Sri Venkata
authors.initials: SV
authors.lastname: Madhu
authors.forename: Raman K
authors.initials: RK
authors.lastname: Marwaha
authors.forename: Analabha
authors.initials: A
authors.lastname: Basu
authors.forename: Vinod
authors.initials: V
authors.lastname: Scaria
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: Radha
authors.initials: R
authors.lastname: Venkatesan
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Mohan
authors.forename: Nikhil
authors.initials: N
authors.lastname: Tandon
authors.forename: Dwaipayan
authors.initials: D
authors.lastname: Bharadwaj
mesh_terms: D000368:Aged; D044466:Asian People; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007194:India; D007333:Insulin Resistance; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D044465:White People
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C579751:TMEM163 protein, human