Quantifying the contribution of dominance deviation effects to complex trait variation in biobank-scale data.
Quantifying the contribution of dominance deviation effects to complex trait variation in biobank-scale data.
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DOI：
10.1016/j.ajhg.2021.03.018
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发表时间：
2021-05-06
影响因子：
9.8
通讯作者：
Sankararaman S
中科院分区：
文献类型：
--
作者：
Pazokitoroudi A;Chiu AM;Burch KS;Pasaniuc B;Sankararaman S
复杂性状中可归因于非加性遗传效应的变异比例一直是一个激烈争论的话题。来自无关个体的基因型和性状数据的生物库规模数据集的可用性开辟了获得非加性遗传效应贡献的精确估计的可能性。我们提出了一种有效的方法来估计一个复杂的性状的变化，可以归因于添加剂（添加剂遗传力）和显性偏差（显性遗传力）的影响，在所有基因型SNP在一个大的收集无关的个人。在广泛的遗传结构，我们的方法产生无偏估计的加性和显性遗传力。我们依次将我们的方法应用于阵列基因型以及估算的基因型（在次要等位基因频率[MAF] > 1%的常见SNP处）和在英国生物库中的291，273名无关白色英国个体中测量的50个数量性状。对这50个性状进行平均，我们发现阵列SNPs的加性遗传力为21.86%，而显性遗传力为0.13%（约为加性遗传力的0.48%），与插补基因型的定性结果相似。我们没有发现显性遗传力的统计学显著证据（占测试的性状数量），并估计显性遗传力不太可能超过1%的性状分析。我们的分析表明显性遗传力对复杂性状变异的贡献有限。
The proportion of variation in complex traits that can be attributed to non-additive genetic effects has been a topic of intense debate. The availability of biobank-scale datasets of genotype and trait data from unrelated individuals opens up the possibility of obtaining precise estimates of the contribution of non-additive genetic effects. We present an efficient method to estimate the variation in a complex trait that can be attributed to additive (additive heritability) and dominance deviation (dominance heritability) effects across all genotyped SNPs in a large collection of unrelated individuals. Over a wide range of genetic architectures, our method yields unbiased estimates of additive and dominance heritability. We applied our method, in turn, to array genotypes as well as imputed genotypes (at common SNPs with minor allele frequency [MAF] > 1%) and 50 quantitative traits measured in 291,273 unrelated white British individuals in the UK Biobank. Averaged across these 50 traits, we find that additive heritability on array SNPs is 21.86% while dominance heritability is 0.13% (about 0.48% of the additive heritability) with qualitatively similar results for imputed genotypes. We find no statistically significant evidence for dominance heritability ( accounting for the number of traits tested) and estimate that dominance heritability is unlikely to exceed 1% for the traits analyzed. Our analyses indicate a limited contribution of dominance heritability to complex trait variation.
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