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

被引：130

作者：

Tabassum, Rubina ^{[1
]}

Chauhan, Ganesh ^{[1
]}

Dwivedi, Om Prakash ^{[1
]}

Mahajan, Anubha ^{[1
]}

Jaiswal, Alok ^{[1
]}

Kaur, Ismeet ^{[1
]}

Bandesh, Khushdeep ^{[1
]}

Singh, Tejbir ^{[1
]}

Mathai, Benan John ^{[1
]}

Pandey, Yogesh ^{[1
]}

Chidambaram, Manickam ^{[2
]}

Sharma, Amitabh ^{[1
]}

Chavali, Sreenivas ^{[1
]}

Sengupta, Shantanu ^{[1
]}

Ramakrishnan, Lakshmi ^{[3
]}

Venkatesh, Pradeep ^{[3
]}

Aggarwal, Sanjay K. ^{[3
]}

Ghosh, Saurabh ^{[4
]}

Prabhakaran, Dorairaj ^{[5
]}

Srinath, Reddy K. ^{[6
]}

Saxena, Madhukar ^{[7
]}

Banerjee, Monisha ^{[7
]}

Mathur, Sandeep ^{[8
]}

Bhansali, Anil ^{[9
]}

Shah, Viral N. ^{[9
]}

Madhu, Sri Venkata ^{[10
]}

Marwaha, Raman K. ^{[11
]}

Basu, Analabha ^{[12
]}

Scaria, Vinod ^{[13
]}

McCarthy, Mark I. ^{[14
,15
,16
]}

Venkatesan, Radha ^{[2
]}

Mohan, Viswanathan ^{[2
]}

Tandon, Nikhil ^{[3
]}

Bharadwaj, Dwaipayan ^{[1
]}

机构：

[1] Inst Genom & Integrat Biol, Genom & Mol Med Unit, Council Sci & Ind Res, Delhi, India

[2] Adv Ctr Genom Diabet, Dept Mol Genet, Madras Diabet Res Fdn, Indian Council Med Res, Chennai, Tamil Nadu, India

[3] All India Inst Med Sci, Dept Endocrinol, New Delhi, India

[4] Indian Stat Inst, Human Genet Unit, Kolkata, India

[5] Ctr Chron Dis Control, New Delhi, India

[6] Publ Hlth Fdn India, New Delhi, India

[7] Univ Lucknow, Dept Zool, Lucknow 226007, Uttar Pradesh, India

[8] SMS Med Coll & Hosp, Dept Endocrinol, Jaipur, Rajasthan, India

[9] Post Grad Inst Med Educ & Res, Dept Endocrinol, Sect 12, Chandigarh, India

[10] Univ Coll Med Sci, Div Endocrinol, Delhi 110095, India

[11] Inst Nucl Med & Allied Sci, Dept Endocrinol & Thyroid Res, Delhi, India

[12] Natl Inst BioMed Genom, Kalyani, W Bengal, India

[13] Inst Genom & Integrat Biol, GN Ramachandran Knowledge Ctr Genome Informat, Council Sci & Ind Res, Delhi, India

[14] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[15] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Churchill Hosp, Oxford, England

[16] Churchill Hosp, Oxford Natl Inst Hlth Res, Biomed Res Ctr, Oxford OX3 7LJ, England

来源：

DIABETES | 2013年 / 62卷 / 03期

基金：

美国国家卫生研究院;

关键词：

INSULIN-RESISTANCE; VARIANTS; GLUCOSE; PROTEIN; DECARBOXYLASE; METAANALYSIS; HOMEOSTASIS; KINASE; RISK; SV31;

D O I：

10.2337/db12-0406

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 X 10(-9)). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 x 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. Diabetes 62:977-986, 2013

引用

页码：977 / 986

页数：10

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