Phenome-wide heritability analysis of the UK Biobank.
Phenome-wide heritability analysis of the UK Biobank.
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DOI：
10.1371/journal.pgen.1006711
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发表时间：
2017-04
期刊：
影响因子：
4.5
通讯作者：
Smoller JW
中科院分区：
文献类型：
--
作者：
Ge T;Chen CY;Neale BM;Sabuncu MR;Smoller JW
遗传力估计提供了关于遗传和环境因素对表型变异的相对贡献的重要信息，并为遗传风险预测模型的实用性提供了上限。最近的技术和统计学的进步，使加性遗传力的估计归因于常见的遗传变异（SNP遗传力）在广泛的表型谱。在这里，我们提出了一种计算和记忆效率的遗传力估计方法，可以处理大样本量，并报告了551个复杂性状的SNP遗传力，这些复杂性状来自大规模，基于人群的英国生物库的中期数据发布（152，736名受试者），包括定量表型和疾病代码。我们证明了常见的遗传变异有助于英国人群中广泛的数量性状和人类疾病，并确定了遗传力受年龄调节的表型（例如，大多数身体测量包括身高和体重指数），性别（例如，血压相关性状）和社会经济地位（教育）。我们的研究代表了英国生物库中第一个全面的全表型遗传力分析，并强调了在解释遗传力时考虑人口特征的重要性。性状的遗传力是指由于个体间遗传变异引起的表型变异的比例。它提供了关于复杂性状的遗传基础的重要信息，并表明表型是否是更具体的统计和分子遗传分析的适当目标。最近的研究利用了越来越普遍的全基因组数据，并记录了遗传性归因于常见的遗传变异的基因分型微阵列捕获的广泛的人类性状。然而，遗传力不是表型的固定属性，并且可以随着遗传背景和环境变化的群体特异性差异而变化。在这里，使用计算和内存高效的遗传力估计方法，我们报告了来自大规模，基于人口的英国生物库的大量性状的遗传力，并首次证明了三个主要人口统计变量（年龄，性别和社会经济地位）的调节作用来自全基因组常见遗传变异的遗传力估计。我们的研究代表了英国生物库中表型谱的第一个综合遗传力分析。
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. Heritability of a trait refers to the proportion of phenotypic variation that is due to genetic variation among individuals. It provides important information about the genetic basis of complex traits and indicates whether a phenotype is an appropriate target for more specific statistical and molecular genetic analyses. Recent studies have leveraged the increasingly ubiquitous genome-wide data and documented the heritability attributable to common genetic variation captured by genotyping microarrays for a wide range of human traits. However, heritability is not a fixed property of a phenotype and can vary with population-specific differences in the genetic background and environmental variation. Here, using a computationally and memory efficient heritability estimation method, we report the heritability for a large number of traits derived from the large-scale, population-based UK Biobank, and, for the first time, demonstrate the moderating effect of three major demographic variables (age, sex and socioeconomic status) on heritability estimates derived from genome-wide common genetic variation. Our study represents the first comprehensive heritability analysis across the phenotypic spectrum in the UK Biobank.