Assessing the Contribution Family Data Can Make to Case-Control Studies of Rare Variants
Assessing the Contribution Family Data Can Make to Case-Control Studies of Rare Variants
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DOI：
10.1111/j.1469-1809.2011.00660.x
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发表时间：
2011-09-01
影响因子：
1.9
通讯作者：
Curtis, David
中科院分区：
文献类型：
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作者：
Curtis, David
当病原变异很罕见时，即使在病例中，拥有变异的受试者的比例也可能很低，这意味着可能需要非常大的样本才能最终证明一种效应的证据。病例对照样本中受试者的亲属可能提供有用的额外信息。在MFLINK中实施的无模型连锁分析方法被应用于纳入连锁不平衡(LD)参数，以测试假设的致病变异对具有疾病基因的完全LD的影响。研究了将携带该变异的病例和对照的亲属加入分析的效果。当合并具有该变异的病例的受影响的兄弟姐妹或表亲时，他们对所获得的结果有很大的影响。参与的证据如预期的那样增加或减少，这取决于亲属本身是否被发现拥有变异。与仅仅增加标准病例对照样本的大小相比，影响的大小是很大的。受影响的亲属为解释罕见变异的病例对照研究提供了宝贵的资源。该方法能够包含其他亲缘关系类型，并能处理复杂的家系。
When pathogenic variants are rare then even among cases the proportion of subjects possessing a variant might be low, meaning that very large samples might be required to conclusively demonstrate evidence of an effect. Relatives of subjects within a case-control sample might provide useful additional information.The method of model-free linkage analysis implemented in MFLINK was adapted to incorporate linkage disequilibrium (LD) parameters in order to test for an effect of a putative pathogenic variant in complete LD with a disease locus. The effect of adding in to the analysis relatives of cases and controls found to carry the variant was investigated.When affected siblings or cousins of cases possessing the variant were incorporated they had a large effect on the results obtained. The evidence for involvement increased or reduced as expected, depending on whether or not the relatives themselves were found to possess the variant. The size of the effect was large relative to that expected from just increasing the size of a standard case-control sample.Affected relatives offer a valuable resource to assist the interpretation of case-control studies of rare variants. The method is capable of including other relative types and can deal with complex pedigrees.