Ge Tian, Chen Chia-Yen, Neale Benjamin M, Sabuncu Mert R, Smoller Jordan W
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital / Harvard Medical School, Charlestown, MA, United States of America.
Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States of America.
PLoS Genet. 2017 Apr 7;13(4):e1006711. doi: 10.1371/journal.pgen.1006711. eCollection 2017 Apr.
Heritability estimation provides important information about the relative contribution of genetic and environmental factors to phenotypic variation, and provides an upper bound for the utility of genetic risk prediction models. Recent technological and statistical advances have enabled the estimation of additive heritability attributable to common genetic variants (SNP heritability) across a broad phenotypic spectrum. Here, we present a computationally and memory efficient heritability estimation method that can handle large sample sizes, and report the SNP heritability for 551 complex traits derived from the interim data release (152,736 subjects) of the large-scale, population-based UK Biobank, comprising both quantitative phenotypes and disease codes. We demonstrate that common genetic variation contributes to a broad array of quantitative traits and human diseases in the UK population, and identify phenotypes whose heritability is moderated by age (e.g., a majority of physical measures including height and body mass index), sex (e.g., blood pressure related traits) and socioeconomic status (education). Our study represents the first comprehensive phenome-wide heritability analysis in the UK Biobank, and underscores the importance of considering population characteristics in interpreting heritability.
遗传力估计提供了关于遗传和环境因素对表型变异相对贡献的重要信息，并为遗传风险预测模型的效用提供了上限。最近的技术和统计进展使得能够在广泛的表型范围内估计归因于常见遗传变异的加性遗传力（单核苷酸多态性遗传力）。在此，我们提出了一种计算和内存高效的遗传力估计方法，该方法可以处理大样本量，并报告了来自大规模、基于人群的英国生物银行中期数据发布（152,736名受试者）的551个复杂性状的单核苷酸多态性遗传力，这些性状包括定量表型和疾病编码。我们证明，常见遗传变异对英国人群中的一系列定量性状和人类疾病有贡献，并确定了其遗传力受年龄（如包括身高和体重指数在内的大多数身体测量指标）、性别（如与血压相关的性状）和社会经济地位（教育程度）影响的表型。我们的研究是英国生物银行中首次全面的全表型组遗传力分析，并强调了在解释遗传力时考虑人群特征的重要性。
