在47万名英国生物库参与者中,对罕见的编码变体的加权负担分析描述了对超脂血症风险的影响
1UCL Genetics Institute, University College London, London, UK. d.curtis@ucl.ac.uk.
六个基因中的罕见遗传变异,包括LDLR和PCSK9,与高脂血症风险有显著的关联. 一些变异增加了风险,而另一些则是保护性的,为新疗法提供了对分子机制的洞察.
科学领域:
- 遗传学 是一个遗传学.
- 心血管疾病 心血管疾病
- 代谢障碍 代谢障碍 代谢障碍
背景情况:
- 之前的外体全域关联研究 (EWAS) 在20万名英国生物库参与者中确定了与超脂血症相关的四个基因.
- 另外43个基因显示与高脂血症有暗示性关联 (p < 0.001).
研究的目的:
- 为了研究47个先前突出显示的基因与超脂血症的关联,在扩大的英国生物银行队列中.
- 在多次测试纠正后,识别与超脂血症相关的统计学上显著的基因.
主要方法:
- 对来自47万名英国生物库参与者的外体序列数据进行了加权负担分析.
- 统计分析以评估罕见编码变体与高脂血症之间的关联.
主要成果:
- 在多次测试纠正后,六个基因 (LDLR,PCSK9,APOC3,ANGPTL3,ABCG5,NPC1L1) 显著与高脂血症相关.
- 在LDLR和ABCG5的变体与高脂血症风险增加有关,而在PCSK9,APOC3,ANGPTL3和NPC1L1的变体是保护性的.
- IFITM5没有涉及到扩展队列.
结论:
- 六个关键基因中的罕见变异对高脂血症有重大影响.
- 了解这些遗传关联可以阐明分子途径,并为高脂血症的新型治疗策略的开发提供信息.
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