Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
Eur J Hum Genet. 2010 May;18(5):569-74. doi: 10.1038/ejhg.2009.210. Epub 2009 Nov 25.
The Saami from Fennoscandia are believed to represent an ancient, genetically isolated population with no evidence of population expansion. Theoretical work has indicated that under this demographic scenario, extensive linkage disequilibrium (LD) is generated by genetic drift. Therefore, it has been suggested that the Saami would be particularly suited for genetic association studies, offering a substantial power advantage and allowing more economic study designs. However, no study has yet assessed this claim. As part of a GWAS for a complex trait, we evaluated the relative power for association studies of common variants in the Finnish Saami. LD patterns in the Saami were very similar to those in the non-African HapMap reference panels. Haplotype diversity was reduced and, on average, levels of LD were higher in the Saami as compared with those in the HapMap panels. However, using a 'hidden' SNP approach we show that this does not translate into a power gain in association studies. Contrary to earlier claims, we show that for a given set of common SNPs, genomic coverage attained in the Saami is similar to that in the non-African HapMap panels. Nevertheless, the reduced haplotype diversity could potentially facilitate gene identification, especially if multiple rare variants play a role in disease etiology. Our results further indicate that the HapMap is a useful resource for genetic studies in the Saami.
来自芬诺斯堪的纳维亚的萨米人被认为是一个古老的、遗传上孤立的群体,没有人口扩张的证据。理论工作表明,在这种人口统计情况下,遗传漂变产生了广泛的连锁不平衡(LD)。因此,有人建议萨米人特别适合进行遗传关联研究,提供了实质性的优势,并允许更经济的研究设计。然而,迄今为止,还没有研究评估这一说法。作为一项复杂特征全基因组关联研究(GWAS)的一部分,我们评估了在芬兰萨米人中常见变体关联研究的相对效力。萨米人的 LD 模式与非非洲 HapMap 参考面板非常相似。萨米人的单倍型多样性降低,与 HapMap 面板相比,LD 水平平均更高。然而,使用“隐藏”SNP 方法,我们表明这并不会转化为关联研究中的效力增益。与早期的说法相反,我们表明,对于给定的一组常见 SNP,在萨米人中获得的基因组覆盖与非非洲 HapMap 面板中的覆盖相似。尽管如此,降低的单倍型多样性可能会促进基因的识别,特别是如果多个罕见变体在疾病病因学中起作用。我们的结果进一步表明,HapMap 是萨米人遗传研究的有用资源。