A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants
A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants
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DOI：
10.1126/science.1142382
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发表时间：
2007-06-01
期刊：
影响因子：
56.9
通讯作者：
Boehnke, Michael
中科院分区：
文献类型：
--
作者：
Scott, Laura J.;Mohlke, Karen L.;Boehnke, Michael
识别增加人类 2 型糖尿病 (T2D) 风险的基因变异一直是一项艰巨的挑战。采用全基因组关联策略，我们对 1161 名芬兰 T2D 病例和 1174 名芬兰正常耐糖 (NGT) 对照进行了基因分型，这些对照具有超过 315,000 个单核苷酸多态性 (SNP)，并估算了另外超过 200 万个常染色体 SNP 的基因型。我们对这些 SNP 进行了关联分析，以确定易患 T2D 的遗传变异，将我们的 T2D 关联结果与两项类似研究的结果进行比较，并对另外 1215 例芬兰 T2D 病例和 1258 例芬兰 NGT 对照中的 80 个 SNP 进行了基因分型。我们在染色体 11p12 的基因间区域中鉴定了 T2D 相关变异，有助于鉴定 IGF2BP2 和 CDKAL1 基因附近以及 CDKN2A 和 CDKN2B 区域附近的 T2D 相关变异，并确认 TCF7L2、SLC30A8、HHEX、FTO、PPARG 和 KCNJ11 附近的变异与 T2D 相关 风险。这使得目前已确定的 T2D 基因座数量达到至少 10 个。
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.