Combining evidence of natural selection with association analysis increases power to detect malaria-resistance variants
Combining evidence of natural selection with association analysis increases power to detect malaria-resistance variants
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DOI：
10.1086/519221
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发表时间：
2007-08-01
影响因子：
9.8
通讯作者：
Reich, David
中科院分区：
文献类型：
--
作者：
Ayodo, George;Price, Alkes L.;Reich, David
检测疾病变异的统计能力可以通过根据自然选择的证据对候选者进行加权来提高。为了证明这一理论思想在实践中的工作，我们进行了一项关联研究的10个假定的耐药变异体在471例严重疟疾病例和474个控制从肯尼亚卢奥。我们复制了HBB（P = 0.0008）和CD 36（P = 0.03）的相关性，但也表明Luo人和约鲁巴人（历史上曾接触过疟疾）与马赛人和基库尤（未接触过疟疾）之间的频率存在异常差异。这从经验上证明，将关联分析与自然选择的证据相结合，可以增加检测风险变异的能力，其数量级高达HBB的P = 0.000018，CD 36的P = 0.00043。
Statistical power to detect disease variants can be increased by weighting candidates by their evidence of natural selection. To demonstrate that this theoretical idea works in practice, we performed an association study of 10 putative resistance variants in 471 severe malaria cases and 474 controls from the Luo in Kenya. We replicated associations at HBB (P =.0008) and CD36 (P =.03) but also showed that the same variants are unusually differentiated in frequency between the Luo and Yoruba (who historically have been exposed to malaria) and the Masai and Kikuyu (who have not been exposed). This empirically demonstrates that combining association analysis with evidence of natural selection can increase power to detect risk variants by orders of magnitude-up to P =.000018 for HBB and P =.00043 for CD36.