An Icelandic example of the impact of population structure on association studies
An Icelandic example of the impact of population structure on association studies
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DOI：
10.1038/ng1492
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发表时间：
2005-01-01
期刊：
影响因子：
30.8
通讯作者：
Stefánsson, K
中科院分区：
文献类型：
--
作者：
Helgason, A;Yngvadóttir, B;Stefánsson, K
人口结构对确定人类常见疾病的遗传变异的关联研究的影响是一个越来越受关注的问题（1-4）。当等位基因频率在亚群中存在显著差异，而在病例和对照中没有得到平等代表时，可能会得到等位基因与疾病表型之间的虚假关联，或者忽略真正的关联。人口结构甚至会影响精心设计的研究，并可能影响关联结果的有效性（1,2）。大多数研究设计通过从具有相同国籍或自我报告的种族背景的群体中取样和控制来解决这个问题，并隐含地假设在这些群体中不存在子结构。我们使用广泛的家谱和遗传数据检查了冰岛基因库中的种群结构。我们的研究结果表明，即使在一个相对同质的(5)遗传分离物(6)中，采样策略也需要考虑到子结构。在更大的人群中，这一点可能更为重要。
The impact of population structure on association studies undertaken to identify genetic variants underlying common human diseases is an issue of growing interest(1-4). Spurious associations of alleles with disease phenotypes may be obtained or true associations overlooked when allele frequencies differ notably among subpopulations that are not represented equally among cases and controls. Population structure influences even carefully designed studies and can affect the validity of association results(1,2). Most study designs address this problem by sampling cases and controls from groups that share the same nationality or self-reported ethnic background, with the implicit assumption that no substructure exists within such groups. We examined population structure in the Icelandic gene pool using extensive genealogical and genetic data. Our results indicate that sampling strategies need to take account of substructure even in a relatively homogenous(5) genetic isolate(6). This will probably be even more important in larger populations.