从全基因组关联研究中估计效应大小分布及其对未来发现的影响。

Estimation of effect size distribution from genome-wide association studies and implications for future discoveries.

机构信息

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Rockville, Maryland, USA.

出版信息

Nat Genet. 2010 Jul;42(7):570-5. doi: 10.1038/ng.610. Epub 2010 Jun 20.

Abstract

We report a set of tools to estimate the number of susceptibility loci and the distribution of their effect sizes for a trait on the basis of discoveries from existing genome-wide association studies (GWASs). We propose statistical power calculations for future GWASs using estimated distributions of effect sizes. Using reported GWAS findings for height, Crohn's disease and breast, prostate and colorectal (BPC) cancers, we determine that each of these traits is likely to harbor additional loci within the spectrum of low-penetrance common variants. These loci, which can be identified from sufficiently powerful GWASs, together could explain at least 15-20% of the known heritability of these traits. However, for BPC cancers, which have modest familial aggregation, our analysis suggests that risk models based on common variants alone will have modest discriminatory power (63.5% area under curve), even with new discoveries.

摘要

我们报告了一组工具,用于根据现有全基因组关联研究 (GWAS) 的发现,估计性状的易感基因座数量及其效应大小的分布。我们提出了使用估计的效应大小分布进行未来 GWAS 的统计功效计算。使用报告的身高、克罗恩病和乳腺癌、前列腺癌和结直肠癌 (BPC) 的 GWAS 发现,我们确定这些性状中的每一个都可能在低外显率常见变体范围内具有其他基因座。这些基因座可以从足够强大的 GWAS 中识别出来,它们加起来至少可以解释这些性状已知遗传率的 15-20%。然而,对于家族聚集程度适中的 BPC 癌症,我们的分析表明,即使有新的发现,仅基于常见变异的风险模型的判别能力也很有限(曲线下面积为 63.5%)。

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