دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.
المؤلفون: Tabassum, Rubina, Chauhan, Ganesh, Dwivedi, Om Prakash, Mahajan, Anubha, Jaiswal, Alok, Kaur, Ismeet, Bandesh, Khushdeep, Singh, Tejbir, Mathai, Benan John, Pandey, Yogesh, Chidambaram, Manickam, 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, DIAGRAM, INDICO, Venkatesan, Radha, Mohan, Viswanathan, Tandon, Nikhil, Bharadwaj, Dwaipayan
بيانات النشر: American Diabetes Association
//dx.doi.org/10.2337/db12-0406
Diabetes
سنة النشر: 2013
المجموعة: Apollo - University of Cambridge Repository
مصطلحات موضوعية: Aged, Asian People, Chromosomes, Human, Pair 2, Diabetes Mellitus, Type 2, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, India, Insulin Resistance, Membrane Proteins, Middle Aged, Nerve Tissue Proteins, Polymorphism, Single Nucleotide, White People
الوصف: 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.
نوع الوثيقة: article in journal/newspaper
وصف الملف: Print-Electronic; application/pdf
اللغة: English
العلاقة: https://www.repository.cam.ac.uk/handle/1810/273427Test
DOI: 10.17863/CAM.20457
الإتاحة: https://doi.org/10.17863/CAM.20457Test
https://www.repository.cam.ac.uk/handle/1810/273427Test
حقوق: Attribution-NonCommercial-NoDerivatives 4.0 International ; http://creativecommons.org/licenses/by-nc-nd/4.0Test/
رقم الانضمام: edsbas.1BAB46CF
قاعدة البيانات: BASE