Author(s): Parra EJ, Below JE, Krithika S, Valladares A, Barta JL, et al.
Aims/hypothesis: We report a genome-wide association study of type 2 diabetes in an admixed sample from Mexico City and describe the results of a meta-analysis of this study and another genome-wide scan in a Mexican-American sample from Starr County, TX, USA. The top signals observed in this meta-analysis were followed up in the Diabetes Genetics Replication and Meta-analysis Consortium (DIAGRAM) and DIAGRAM+ datasets.
Methods: We analysed 967 cases and 343 normoglycaemic controls. The samples were genotyped with the Affymetrix Genome-wide Human SNP array 5.0. Associations of genotyped and imputed markers with type 2 diabetes were tested using a missing data likelihood score test. A fixed-effects meta-analysis including 1,804 cases and 780 normoglycaemic controls was carried out by weighting the effect estimates by their inverse variances.
Results: In the meta-analysis of the two Hispanic studies, markers showing suggestive associations (p < 10(-5)) were identified in two known diabetes genes, HNF1A and KCNQ1, as well as in several additional regions. Meta-analysis of the two Hispanic studies and the recent DIAGRAM+ dataset identified genome-wide significant signals (p < 5 × 10(-8)) within or near the genes HNF1A and CDKN2A/CDKN2B, as well as suggestive associations in three additional regions, IGF2BP2, KCNQ1 and the previously unreported C14orf70.
Conclusions/interpretation: We observed numerous regions with suggestive associations with type 2 diabetes. Some of these signals correspond to regions described in previous studies. However, many of these regions could not be replicated in the DIAGRAM datasets. It is critical to carry out additional studies in Hispanic and American Indian populations, which have a high prevalence of type 2 diabetes.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/21573907
Author(s): Gerich JE
Author(s): Stumvoll M, Goldstein BJ, van Haeften TW
Author(s): Dey L, Attele AS, Yuan CS
Author(s): Chen L, Magliano DJ, Zimmet PZ
Author(s): International Diabetes Federation
Author(s): Harcourt BE, Penfold SA, Forbes JM
Author(s): Wild S, Roglic G, Green A, Sicree R, King H
Author(s): Shera AS, Jawad F, Maqsood A
Author(s): Tattersall RB, Fajans SS
Author(s): Shields BM, Hicks S, Shepherd MH, Colclough K, Hattersley AT, et al.
Author(s): Kanwal SF, Fazal S, Muhammad Ismail, Nighat Naureen
Author(s): Velho G, Robert JJ
Author(s): Ben Khelifa S, Barboura I, Dandana A, Ferchichi S, Miled A
Author(s): Pittman WB, Acton RT, Barger BO, Bell DS, Go RC, et al.
Author(s): Matejkova-Behanova M
Author(s): Nambam B, Aggarwal S, Jain A
Author(s): Gale EA
Author(s): Fourlanos S, Dotta F, Greenbaum CJ, Palmer JP, Rolandsson O, et al.
Author(s): Cervin C, Lyssenko V, Bakhtadze E, Lindholm E, Nilsson P, et al.
Author(s): Owen KR, McCarthy MI
Author(s): Doria A, Patti ME, Kahn CR
Author(s): Yang L, Zhou X, Luo Y, Sun X, Tang Y, et al.
Author(s): Wheeler E, Barroso I
Author(s): McCarthy MI, Zeggini E
Author(s): Saxena R, Saleheen D, Been LF, Garavito ML, Braun T, et al.
Author(s): Prokopenko I, McCarthy MI, Lindgren CM
Author(s): Sanghera DK, Blackett PR
Author(s): Sladek R, Rocheleau G, Rung J, Dina C, Shen L, et al.
Author(s): Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes of BioMedical Research, Saxena R, Voight BF, et al.
Author(s): Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, et al.
Author(s): Wellcome Trust Case Control Consortium
Author(s): Steinthorsdottir V, Thorleifsson G, Reynisdottir I, Benediktsson R, Jonsdottir T, et al.
Author(s): Omori S, Tanaka Y, Takahashi A, Hirose H, Kashiwagi A, et al.
Author(s): Zeggini E, Scott LJ, Saxena R, Voight BF, Marchini JL, et al.
Author(s): Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, et al.
Author(s): Elbein SC, Das SK, Hallman DM, Hanis CL, Hasstedt SJ
Author(s): Ruchat SM, Elks CE, Loos RJ, Vohl MC, Weisnagel SJ, et al.
Author(s): Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, et al.
Author(s): Been LF, Ralhan S, Wander GS, Mehra NK, Singh J, et al.
Author(s): Rees SD, Hydrie MZ, Shera AS, Kumar S, O'Hare JP, et al.
Author(s): Saxena R, Elbers CC, Guo Y, Peter I, Gaunt TR, et al.
Author(s): Morris AP, Voight BF, Teslovich TM, Ferreira T, Segrè AV, et al.
Author(s): Tsai FJ, Yang CF, Chen CC, Chuang LM, Lu CH, et al.
Author(s): Xiang K, Wang Y, Zheng T, Jia W, Li J, et al.
Author(s): Das SK, Hasstedt SJ, Zhang Z, Elbein SC
Author(s): Love-Gregory LD, Wasson J, Ma J, Jin CH, Glaser B, et al.
Author(s): Silander K, Mohlke KL, Scott LJ, Peck EC, Hollstein P, et al.
Author(s): Helgason A, Pálsson S, Thorleifsson G, Grant SF, Emilsson V, et al.
Author(s): van Vliet-Ostaptchouk JV, Shiri-Sverdlov R, Zhernakova A, Strengman E, van Haeften TW, et al.
Author(s): van Hoek M, Dehghan A, Witteman JC, van Duijn CM, Uitterlinden AG, et al.
Author(s): Marquezine GF, Pereira AC, Sousa AG, Mill JG, Hueb WA, et al.
Author(s): Maeda S, Tsukada S, Kanazawa A, Sekine A, Tsunoda T, et al.
Author(s): Horikawa Y, Oda N, Cox NJ, Li X, Orho-Melander M, et al.
Author(s): Cho YM, Kim TH, Lim S, Choi SH, Shin HD, et al.
Author(s): Hu FB, Meigs JB, Li TY, Rifai N, Manson JE
Author(s): Moller DE
Author(s): Reitman ML, Schadt EE
Author(s): Holstein A, Seeringer A, Kovacs P
Author(s): Shu Y, Sheardown SA, Brown C, Owen RP, Zhang S, et al.
Author(s): Becker ML, Visser LE, van Schaik RH, Hofman A, Uitterlinden AG, et al.
Author(s): Avery P, Mousa SS, Mousa SA
Author(s): Aquilante CL
Author(s): Distefano JK, Watanabe RM
Author(s): Lebovitz HE
Author(s): Schroner Z, Javorsky M, Kozarova M, Tkac I
Author(s): Wolford JK, Vozarova de Courten B
