一项针对芬兰人2型糖尿病的全基因组关联研究发现了多个易感变异体。
A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants.
作者信息
Scott Laura J, Mohlke Karen L, Bonnycastle Lori L, Willer Cristen J, Li Yun, Duren William L, Erdos Michael R, Stringham Heather M, Chines Peter S, Jackson Anne U, Prokunina-Olsson Ludmila, Ding Chia-Jen, Swift Amy J, Narisu Narisu, Hu Tianle, Pruim Randall, Xiao Rui, Li Xiao-Yi, Conneely Karen N, Riebow Nancy L, Sprau Andrew G, Tong Maurine, White Peggy P, Hetrick Kurt N, Barnhart Michael W, Bark Craig W, Goldstein Janet L, Watkins Lee, Xiang Fang, Saramies Jouko, Buchanan Thomas A, Watanabe Richard M, Valle Timo T, Kinnunen Leena, Abecasis Gonçalo R, Pugh Elizabeth W, Doheny Kimberly F, Bergman Richard N, Tuomilehto Jaakko, Collins Francis S, Boehnke Michael
机构信息
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
出版信息
Science. 2007 Jun 1;316(5829):1341-5. doi: 10.1126/science.1142382. Epub 2007 Apr 26.
Identifying the genetic variants that increase the risk of type 2 diabetes (T2D) in humans has been a formidable challenge. Adopting a genome-wide association strategy, we genotyped 1161 Finnish T2D cases and 1174 Finnish normal glucose-tolerant (NGT) controls with >315,000 single-nucleotide polymorphisms (SNPs) and imputed genotypes for an additional >2 million autosomal SNPs. We carried out association analysis with these SNPs to identify genetic variants that predispose to T2D, compared our T2D association results with the results of two similar studies, and genotyped 80 SNPs in an additional 1215 Finnish T2D cases and 1258 Finnish NGT controls. We identify T2D-associated variants in an intergenic region of chromosome 11p12, contribute to the identification of T2D-associated variants near the genes IGF2BP2 and CDKAL1 and the region of CDKN2A and CDKN2B, and confirm that variants near TCF7L2, SLC30A8, HHEX, FTO, PPARG, and KCNJ11 are associated with T2D risk. This brings the number of T2D loci now confidently identified to at least 10.
识别增加人类患2型糖尿病（T2D）风险的基因变异一直是一项艰巨的挑战。我们采用全基因组关联策略，对1161例芬兰T2D患者和1174例芬兰糖耐量正常（NGT）对照进行了基因分型，使用了超过31.5万个单核苷酸多态性（SNP），并对另外超过200万个常染色体SNP进行了基因型填充。我们对这些SNP进行关联分析以识别易患T2D的基因变异，将我们的T2D关联结果与两项类似研究的结果进行比较，并在另外1215例芬兰T2D患者和1258例芬兰NGT对照中对80个SNP进行基因分型。我们在11号染色体p12的基因间区域识别出与T2D相关的变异，有助于在IGF2BP2和CDKAL1基因以及CDKN2A和CDKN2B区域附近识别与T2D相关的变异，并证实TCF7L2、SLC30A8、HHEX、FTO、PPARG和KCNJ11附近的变异与T2D风险相关。这使得目前确定的T2D基因座数量至少增加到10个。
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