Author(s): Elbein SC, Das SK, Hallman DM, Hanis CL, Hasstedt SJ
Objective: We used a single nucleotide polymorphism (SNP) map in a large cohort of 580 African American families to identify regions linked to type 2 diabetes, age of type 2 diabetes diagnosis, and BMI.
Research design and methods: After removing outliers and problematic samples, we conducted linkage analysis using 5,914 SNPs in 1,344 individuals from 530 families. Linkage analysis was conducted using variance components for type 2 diabetes, age of type 2 diabetes diagnosis, and BMI and nonparametric linkage analyses. Ordered subset analyses were conducted ranking on age of type 2 diabetes diagnosis, BMI, waist circumference, waist-to-hip ratio, and amount of European admixture. Admixture mapping was conducted using 4,486 markers not in linkage disequilibrium.
Results: The strongest signal for type 2 diabetes (logarithm of odds [LOD] 4.53) was a broad peak on chromosome 2, with weaker linkage to age of type 2 diabetes diagnosis (LOD 1.82). Type 2 diabetes and age of type 2 diabetes diagnosis were linked to chromosome 13p (3-22 cM; LOD 2.42 and 2.46, respectively). Age of type 2 diabetes diagnosis was linked to 18p (66 cM; LOD 2.96). We replicated previous reports on chromosome 7p (79 cM; LOD 2.93). Ordered subset analysis did not overlap with linkage of unselected families. The best admixture score was on chromosome 12 (90 cM; P = 0.0003).
Conclusions: The linkage regions on chromosomes 7 (27-78 cM) and 18p overlap prior reports, whereas regions on 2p and 13p linkage are novel. Among potential candidate genes implicated are TCF7L1, VAMP5, VAMP8, CDK8, INSIG2, IPF1, PAX8, IL18R1, members of the IL1 and IL1 receptor families, and MAP4K4. These studies provide a complementary approach to genome-wide association scans to identify causative genes for African American diabetes.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/18840782
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): 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): Parra EJ, Below JE, Krithika S, Valladares A, Barta JL, 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
