二型糖尿病的遗传结构
Christian Fuchsberger1,2,3, Jason Flannick4,5, Tanya M Teslovich1
1Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
Nature
|July 12, 2016
概括
较低频率的基因变异不会显著影响2型糖尿病的风险. 大规模测序研究发现常见的变异,而不是罕见的变异,是2型糖尿病倾向的关键.
科学领域:
- 遗传学
- 代谢疾病
背景情况:
- 包括2型糖尿病在内的共同特征的遗传基础仍然不完全理解.
- 全基因组关联研究 (GWAS) 已经发现了许多常见的2型糖尿病变异,但它们只解释了其遗传的一小部分.
研究的目的:
- 研究低频基因变异在2型糖尿病倾向中的作用.
- 测试这些变异导致2型糖尿病遗传性缺失的假设.
主要方法:
- 在患有或没有2型糖尿病的欧洲人中进行了全基因组和外基因组测序.
- 在超过111,000名受试者中使用基因型和归算来扩大样本大小以提高统计能力.
主要成果:
- 与2型糖尿病相关的鉴定变异主要是常见的.
- 大多数已识别的变种都位于之前涉及GWAS的地区.
- 大规模测序数据不支持低频变异在2型糖尿病倾向中的重要作用.
结论:
- 常见的变异,而不是较低的变异,是导致2型糖尿病风险的主要遗传因素.
- 进一步的研究应集中在常见变异在疾病病理生理学中的功能作用上.
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