Genomic inflation factors under polygenic inheritance
Genomic inflation factors under polygenic inheritance
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DOI：
10.1038/ejhg.2011.39
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发表时间：
2011-07-01
影响因子：
5.2
通讯作者：
Visscher, Peter M.
中科院分区：
文献类型：
--
作者：
Yang, Jian;Weedon, Michael N.;Visscher, Peter M.
在全基因组关联研究（GWAS）中，包括种群分层和隐型亲缘关系在内的种群结构可能导致虚假关联。通常，使用从基因组中多个单核苷酸多态性计算的关联的缩放中位数或平均值检验统计量来评估这种影响，然后可以应用“基因组控制”，通过基因组膨胀因子来调整单个位点的检验统计量。已发表的GWAS已经清楚地表明，在广泛的复杂疾病和性状中存在许多潜在的遗传变异位点，这意味着相当大比例的基因组应该显示出测试统计量的膨胀。在这里，我们通过理论、模拟和数据分析表明，在没有人口结构和其他技术人工制品的情况下，但在存在多基因遗传的情况下，预计会出现大量的基因组膨胀。其大小取决于样本量、遗传力、连锁不平衡结构和因果变异的数量。我们的预测与独立样本的经验观察结果一致，这些独立样本大约有4000人，大约有133000人。欧洲人类遗传学杂志（2011）19,807-812；doi: 10.1038 / ejhg.2011.39;2011年3月16日在线发布
Population structure, including population stratification and cryptic relatedness, can cause spurious associations in genome-wide association studies (GWAS). Usually, the scaled median or mean test statistic for association calculated from multiple single-nucleotide-polymorphisms across the genome is used to assess such effects, and 'genomic control' can be applied subsequently to adjust test statistics at individual loci by a genomic inflation factor. Published GWAS have clearly shown that there are many loci underlying genetic variation for a wide range of complex diseases and traits, implying that a substantial proportion of the genome should show inflation of the test statistic. Here, we show by theory, simulation and analysis of data that in the absence of population structure and other technical artefacts, but in the presence of polygenic inheritance, substantial genomic inflation is expected. Its magnitude depends on sample size, heritability, linkage disequilibrium structure and the number of causal variants. Our predictions are consistent with empirical observations on height in independent samples of similar to 4000 and similar to 133 000 individuals. European Journal of Human Genetics (2011) 19, 807-812; doi:10.1038/ejhg.2011.39; published online 16 March 2011