Jakkula Eveliina, Rehnström Karola, Varilo Teppo, Pietiläinen Olli P H, Paunio Tiina, Pedersen Nancy L, deFaire Ulf, Järvelin Marjo-Riitta, Saharinen Juha, Freimer Nelson, Ripatti Samuli, Purcell Shaun, Collins Andrew, Daly Mark J, Palotie Aarno, Peltonen Leena
Department of Molecular Medicine, National Public Health Institute and Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.
Am J Hum Genet. 2008 Dec;83(6):787-94. doi: 10.1016/j.ajhg.2008.11.005.
Although high-density SNP genotyping platforms generate a momentum for detailed genome-wide association (GWA) studies, an offshoot is a new insight into population genetics. Here, we present an example in one of the best-known founder populations by scrutinizing ten distinct Finnish early- and late-settlement subpopulations. By determining genetic distances, homozygosity, and patterns of linkage disequilibrium, we demonstrate that population substructure, and even individual ancestry, is detectable at a very high resolution and supports the concept of multiple historical bottlenecks resulting from consecutive founder effects. Given that genetic studies are currently aiming at identifying smaller and smaller genetic effects, recognizing and controlling for population substructure even at this fine level becomes imperative to avoid confounding and spurious associations. This study provides an example of the power of GWA data sets to demonstrate stratification caused by population history even within a seemingly homogeneous population, like the Finns. Further, the results provide interesting lessons concerning the impact of population history on the genome landscape of humans, as well as approaches to identify rare variants enriched in these subpopulations.
尽管高密度单核苷酸多态性（SNP）基因分型平台为全基因组关联（GWA）的详细研究带来了契机，但由此产生的一个附带成果是对群体遗传学有了新的认识。在此，我们通过仔细研究十个不同的芬兰早期和晚期定居亚群，展示了一个在最著名的奠基者群体之一中的例子。通过确定遗传距离、纯合度和连锁不平衡模式，我们证明群体亚结构乃至个体祖先都能以非常高的分辨率被检测到，并支持了由连续奠基者效应导致多个历史瓶颈的概念。鉴于目前的遗传学研究旨在识别越来越小的遗传效应，认识到并控制即使在如此精细水平上的群体亚结构对于避免混淆和虚假关联变得至关重要。这项研究提供了一个例子，说明GWA数据集能够证明即使在看似同质的群体（如芬兰人）中，群体历史也会导致分层。此外，研究结果为群体历史对人类基因组格局的影响以及识别这些亚群中富集的罕见变异的方法提供了有趣的启示。
