通过利用祖先架构和使用PAGE和UKBB队列的功能注释来评估与肥胖相关的细分映射变异的效率
Mohammad Yaser Anwar1, Mariaelisa Graff2, Heather M Highland2
1Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. myaser@unc.edu.
Human genetics
|September 1, 2023
概括
多祖先精细映射改善了对肥胖的因果变体的识别. 多样化的种群提高了全基因组关联研究 (GWAS) 的效率,减少了功能研究的候选变体.
科学领域:
- 遗传学 遗传学 是一个
- 人口遗传学 人口遗传学
- 基因组流行病学 基因组流行病学
背景情况:
- 全基因组关联研究 (GWAS) 往往缺乏多样性,限制了功能变体的发现.
- 在多祖先队列中精细映射可以增强因果变异的识别.
研究的目的:
- 评估多祖先精细映射是否提高了与欧洲祖先专注研究相比,对功能性查询的变体优先级的效率.
- 评估多样化祖先对肥胖相关特征细化映射的表现的影响.
主要方法:
- 进行了对整个基因组进行比较的关联研究 (GWAS) 和精细映射.
- 来自英国生物银行 (UKBB) 的欧洲祖先数据与来自遗传流行病学人口架构 (PAGE) 联盟的多祖先数据进行了比较.
- 可信集 (CS) 分析了变体数量,编码分数,因果关系的后期概率,并在脂肪组织中与表达量化特征位点 (eQTLs) 重叠.
主要成果:
- 与欧洲祖先UKBB样本相比,在祖先多样化的PAGE样本中进行精细映射产生了较小的可信集 (CS),变异较少.
- 在PAGE中的细映射变体显示出更高的平均编码分数和因果关系的后期概率.
- 在PAGE位点中可信的集合经常含有强大的脂肪组织eQTL或与eQTL更紧密的链接不平衡 (LD) 的变体.
结论:
- 利用祖先多样化的种群显著提高了精细映射效率和性能,以识别与肥胖相关的遗传变异.
- 这种方法减少了随后的功能研究候选变体的数量.
- 肥胖的遗传因果变异在不同人群中存在很大的重叠,表明可概括的遗传机制.
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