在英国样本中对全基因组关联信号进行复制，揭示了2型糖尿病的风险位点。
Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes.
作者信息
Zeggini Eleftheria, Weedon Michael N, Lindgren Cecilia M, Frayling Timothy M, Elliott Katherine S, Lango Hana, Timpson Nicholas J, Perry John R B, Rayner Nigel W, Freathy Rachel M, Barrett Jeffrey C, Shields Beverley, Morris Andrew P, Ellard Sian, Groves Christopher J, Harries Lorna W, Marchini Jonathan L, Owen Katharine R, Knight Beatrice, Cardon Lon R, Walker Mark, Hitman Graham A, Morris Andrew D, Doney Alex S F, McCarthy Mark I, Hattersley Andrew T
机构信息
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, UK.
出版信息
Science. 2007 Jun 1;316(5829):1336-41. doi: 10.1126/science.1142364. Epub 2007 Apr 26.
The molecular mechanisms involved in the development of type 2 diabetes are poorly understood. Starting from genome-wide genotype data for 1924 diabetic cases and 2938 population controls generated by the Wellcome Trust Case Control Consortium, we set out to detect replicated diabetes association signals through analysis of 3757 additional cases and 5346 controls and by integration of our findings with equivalent data from other international consortia. We detected diabetes susceptibility loci in and around the genes CDKAL1, CDKN2A/CDKN2B, and IGF2BP2 and confirmed the recently described associations at HHEX/IDE and SLC30A8. Our findings provide insight into the genetic architecture of type 2 diabetes, emphasizing the contribution of multiple variants of modest effect. The regions identified underscore the importance of pathways influencing pancreatic beta cell development and function in the etiology of type 2 diabetes.
2型糖尿病发病过程中涉及的分子机制目前仍知之甚少。我们以威康信托病例对照研究联盟生成的1924例糖尿病患者和2938例人群对照的全基因组基因型数据为起点，通过分析另外3757例病例和5346例对照，并将我们的研究结果与其他国际合作组的等效数据整合，着手检测可重复的糖尿病关联信号。我们在CDKAL1、CDKN2A/CDKN2B和IGF2BP2基因及其周围区域检测到了糖尿病易感位点，并证实了最近报道的HHEX/IDE和SLC30A8基因的关联。我们的研究结果为2型糖尿病的遗传结构提供了见解，强调了多个中等效应变异的作用。所确定的区域突出了影响胰腺β细胞发育和功能的通路在2型糖尿病病因学中的重要性。
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