Department of Medicine, Lung Biology Center, University of California San Francisco, San Francisco, CA, USA.
PLoS Genet. 2013 May;9(5):e1003520. doi: 10.1371/journal.pgen.1003520. Epub 2013 May 30.
Important knowledge about the determinants of complex human phenotypes can be obtained from the estimation of heritability, the fraction of phenotypic variation in a population that is determined by genetic factors. Here, we make use of extensive phenotype data in Iceland, long-range phased genotypes, and a population-wide genealogical database to examine the heritability of 11 quantitative and 12 dichotomous phenotypes in a sample of 38,167 individuals. Most previous estimates of heritability are derived from family-based approaches such as twin studies, which may be biased upwards by epistatic interactions or shared environment. Our estimates of heritability, based on both closely and distantly related pairs of individuals, are significantly lower than those from previous studies. We examine phenotypic correlations across a range of relationships, from siblings to first cousins, and find that the excess phenotypic correlation in these related individuals is predominantly due to shared environment as opposed to dominance or epistasis. We also develop a new method to jointly estimate narrow-sense heritability and the heritability explained by genotyped SNPs. Unlike existing methods, this approach permits the use of information from both closely and distantly related pairs of individuals, thereby reducing the variance of estimates of heritability explained by genotyped SNPs while preventing upward bias. Our results show that common SNPs explain a larger proportion of the heritability than previously thought, with SNPs present on Illumina 300K genotyping arrays explaining more than half of the heritability for the 23 phenotypes examined in this study. Much of the remaining heritability is likely to be due to rare alleles that are not captured by standard genotyping arrays.
复杂人类表型的决定因素的重要知识可以通过遗传力的估计获得，遗传力是群体中由遗传因素决定的表型变异的分数。在这里，我们利用冰岛广泛的表型数据、长程相位基因型和全人群系谱数据库，在 38167 个人的样本中研究了 11 种定量表型和 12 种二分表型的遗传力。大多数先前的遗传力估计值都是从基于家庭的方法（如双胞胎研究）中得出的，这些方法可能由于上位性相互作用或共享环境而向上偏倚。我们基于密切和远距离相关个体的遗传力估计值明显低于先前的研究。我们检查了一系列关系的表型相关性，从兄弟姐妹到第一代表亲，发现这些相关个体中过多的表型相关性主要是由于共享环境，而不是显性或上位性。我们还开发了一种新的方法来共同估计狭义遗传力和由基因分型 SNP 解释的遗传力。与现有方法不同，这种方法允许使用密切和远距离相关个体的信息，从而减少由基因分型 SNP 解释的遗传力估计值的方差，同时防止向上偏倚。我们的结果表明，常见的 SNP 解释了比以前认为的更大比例的遗传力，Illumina 300K 基因分型阵列上的 SNP 解释了本研究中检查的 23 种表型中超过一半的遗传力。其余大部分遗传力可能归因于标准基因分型阵列无法捕获的稀有等位基因。
