Genome-wide association study for type 2 diabetes in indians identifies a new susceptibility locus at 2q21

Rubina Tabassum, Ganesh Chauhan, Om Prakash Dwivedi, Anubha Mahajan, Alok Jaiswal, Ismeet Kaur, Khushdeep Bandesh, Tejbir Singh, Benan John Mathai, Yogesh Pandey, Chidambaram Manickam, Amitabh Sharma, Sreenivas Chavali, Shantanu Sengupta, Lakshmi Ramakrishnan, Pradeep Venkatesh, Sanjay K. Aggarwal, Saurabh Ghosh, Dorairaj Prabhakaran, Reddy K. SrinathMadhukar Saxena, Monisha Banerjee, Sandeep Mathur, Anil Bhansali, Viral N. Shah, Sri Venkata Madhu, Raman K. Marwaha, Analabha Basu, Vinod Scaria, Mark I. McCarthy, Radha Venkatesan, Viswanathan Mohan, Nikhil Tandon, Dwaipayan Bharadwaj

Research output: Contribution to journalArticle

97 Citations (Scopus)

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 3 1029). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 3 10212) 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.

Original languageEnglish
Pages (from-to)977-986
Number of pages10
JournalDiabetes
Volume62
Issue number3
DOIs
Publication statusPublished - Mar 2013
Externally publishedYes

Fingerprint

Genome-Wide Association Study
Type 2 Diabetes Mellitus
Odds Ratio
Insulin
Nervous System Diseases
Population
Insulin Resistance
Life Style
Fasting

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Tabassum, R., Chauhan, G., Dwivedi, O. P., Mahajan, A., Jaiswal, A., Kaur, I., ... Bharadwaj, D. (2013). Genome-wide association study for type 2 diabetes in indians identifies a new susceptibility locus at 2q21. Diabetes, 62(3), 977-986. https://doi.org/10.2337/db12-0406

Genome-wide association study for type 2 diabetes in indians identifies a new susceptibility locus at 2q21. / Tabassum, Rubina; Chauhan, Ganesh; Dwivedi, Om Prakash; Mahajan, Anubha; Jaiswal, Alok; Kaur, Ismeet; Bandesh, Khushdeep; Singh, Tejbir; Mathai, Benan John; Pandey, Yogesh; Manickam, Chidambaram; Sharma, Amitabh; Chavali, Sreenivas; Sengupta, Shantanu; Ramakrishnan, Lakshmi; Venkatesh, Pradeep; Aggarwal, Sanjay K.; Ghosh, Saurabh; Prabhakaran, Dorairaj; Srinath, Reddy K.; Saxena, Madhukar; Banerjee, Monisha; Mathur, Sandeep; Bhansali, Anil; Shah, Viral N.; Madhu, Sri Venkata; Marwaha, Raman K.; Basu, Analabha; Scaria, Vinod; McCarthy, Mark I.; Venkatesan, Radha; Mohan, Viswanathan; Tandon, Nikhil; Bharadwaj, Dwaipayan.

In: Diabetes, Vol. 62, No. 3, 03.2013, p. 977-986.

Research output: Contribution to journalArticle

Tabassum, R, Chauhan, G, Dwivedi, OP, Mahajan, A, Jaiswal, A, Kaur, I, Bandesh, K, Singh, T, Mathai, BJ, Pandey, Y, Manickam, C, Sharma, A, Chavali, S, Sengupta, S, Ramakrishnan, L, Venkatesh, P, Aggarwal, SK, Ghosh, S, Prabhakaran, D, Srinath, RK, Saxena, M, Banerjee, M, Mathur, S, Bhansali, A, Shah, VN, Madhu, SV, Marwaha, RK, Basu, A, Scaria, V, McCarthy, MI, Venkatesan, R, Mohan, V, Tandon, N & Bharadwaj, D 2013, 'Genome-wide association study for type 2 diabetes in indians identifies a new susceptibility locus at 2q21', Diabetes, vol. 62, no. 3, pp. 977-986. https://doi.org/10.2337/db12-0406
Tabassum R, Chauhan G, Dwivedi OP, Mahajan A, Jaiswal A, Kaur I et al. Genome-wide association study for type 2 diabetes in indians identifies a new susceptibility locus at 2q21. Diabetes. 2013 Mar;62(3):977-986. https://doi.org/10.2337/db12-0406
Tabassum, Rubina ; Chauhan, Ganesh ; Dwivedi, Om Prakash ; Mahajan, Anubha ; Jaiswal, Alok ; Kaur, Ismeet ; Bandesh, Khushdeep ; Singh, Tejbir ; Mathai, Benan John ; Pandey, Yogesh ; Manickam, Chidambaram ; Sharma, Amitabh ; Chavali, Sreenivas ; Sengupta, Shantanu ; Ramakrishnan, Lakshmi ; Venkatesh, Pradeep ; Aggarwal, Sanjay K. ; Ghosh, Saurabh ; Prabhakaran, Dorairaj ; Srinath, Reddy K. ; Saxena, Madhukar ; Banerjee, Monisha ; Mathur, Sandeep ; Bhansali, Anil ; Shah, Viral N. ; Madhu, Sri Venkata ; Marwaha, Raman K. ; Basu, Analabha ; Scaria, Vinod ; McCarthy, Mark I. ; Venkatesan, Radha ; Mohan, Viswanathan ; Tandon, Nikhil ; Bharadwaj, Dwaipayan. / Genome-wide association study for type 2 diabetes in indians identifies a new susceptibility locus at 2q21. In: Diabetes. 2013 ; Vol. 62, No. 3. pp. 977-986.
@article{266a423bc6e64afb917257909689f79c,
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 3 1029). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 3 10212) 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.",
author = "Rubina Tabassum and Ganesh Chauhan and Dwivedi, {Om Prakash} and Anubha Mahajan and Alok Jaiswal and Ismeet Kaur and Khushdeep Bandesh and Tejbir Singh and Mathai, {Benan John} and Yogesh Pandey and Chidambaram Manickam and Amitabh Sharma and Sreenivas Chavali and Shantanu Sengupta and Lakshmi Ramakrishnan and Pradeep Venkatesh and Aggarwal, {Sanjay K.} and Saurabh Ghosh and Dorairaj Prabhakaran and Srinath, {Reddy K.} and Madhukar Saxena and Monisha Banerjee and Sandeep Mathur and Anil Bhansali and Shah, {Viral N.} and Madhu, {Sri Venkata} and Marwaha, {Raman K.} and Analabha Basu and Vinod Scaria and McCarthy, {Mark I.} and Radha Venkatesan and Viswanathan Mohan and Nikhil Tandon and Dwaipayan Bharadwaj",
year = "2013",
month = "3",
doi = "10.2337/db12-0406",
language = "English",
volume = "62",
pages = "977--986",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "3",

}

TY - JOUR

T1 - Genome-wide association study for type 2 diabetes in indians identifies a new susceptibility locus at 2q21

AU - Tabassum, Rubina

AU - Chauhan, Ganesh

AU - Dwivedi, Om Prakash

AU - Mahajan, Anubha

AU - Jaiswal, Alok

AU - Kaur, Ismeet

AU - Bandesh, Khushdeep

AU - Singh, Tejbir

AU - Mathai, Benan John

AU - Pandey, Yogesh

AU - Manickam, Chidambaram

AU - Sharma, Amitabh

AU - Chavali, Sreenivas

AU - Sengupta, Shantanu

AU - Ramakrishnan, Lakshmi

AU - Venkatesh, Pradeep

AU - Aggarwal, Sanjay K.

AU - Ghosh, Saurabh

AU - Prabhakaran, Dorairaj

AU - Srinath, Reddy K.

AU - Saxena, Madhukar

AU - Banerjee, Monisha

AU - Mathur, Sandeep

AU - Bhansali, Anil

AU - Shah, Viral N.

AU - Madhu, Sri Venkata

AU - Marwaha, Raman K.

AU - Basu, Analabha

AU - Scaria, Vinod

AU - McCarthy, Mark I.

AU - Venkatesan, Radha

AU - Mohan, Viswanathan

AU - Tandon, Nikhil

AU - Bharadwaj, Dwaipayan

PY - 2013/3

Y1 - 2013/3

N2 - 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 3 1029). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 3 10212) 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.

AB - 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 3 1029). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 3 10212) 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.

UR - http://www.scopus.com/inward/record.url?scp=84874418247&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84874418247&partnerID=8YFLogxK

U2 - 10.2337/db12-0406

DO - 10.2337/db12-0406

M3 - Article

C2 - 23209189

AN - SCOPUS:84874418247

VL - 62

SP - 977

EP - 986

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 3

ER -