Mendelian imputation of parental genotypes improves estimates of direct genetic effects.
Mendelian imputation of parental genotypes improves estimates of direct genetic effects.
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DOI：
10.1038/s41588-022-01085-0
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发表时间：
2022-06
期刊：
影响因子：
30.8
通讯作者：
Kong, Augustine
中科院分区：
文献类型：
--
作者：
Young, Alexander, I;Nehzati, Seyed Moeen;Benonisdottir, Stefania;Okbay, Aysu;Jayashankar, Hariharan;Lee, Chanwook;Cesarini, David;Benjamin, Daniel J.;Turley, Patrick;Kong, Augustine
全基因组关联研究（GWAS）估计的效应包括个体中等位基因对该个体的影响（直接遗传效应），间接遗传效应（例如，父母中等位基因通过环境对后代的影响）和混淆偏倚。家庭内的遗传变异是随机的，使无偏估计的直接遗传效应时，父母的基因分型。然而，亲本基因型往往缺失。我们介绍了一种方法，插补缺失的亲本基因型和估计直接的遗传效应。我们的方法，在软件包snipar（父母的单核苷酸插补）中实现，比现有的方法更精确地估计直接遗传效应。使用来自英国生物库的39，614名至少有一个基因分型兄弟姐妹/父母的个体，我们估计了9种表型的直接遗传效应与标准GWAS效应之间的相关性，包括教育程度（r = 0.739，标准误（s.e.））= 0.086）和认知能力（r = 0.490，s.e. = 0.086）。我们的研究结果表明，在标准GWAS的一些表型的实质性混杂偏倚。snipar是一个软件包，用于估算缺失的亲本基因型和估计直接遗传效应。英国生物库数据的应用表明，标准全基因组关联研究设计估计的效应对某些表型具有混淆偏倚。
Effects estimated by genome-wide association studies (GWASs) include effects of alleles in an individual on that individual (direct genetic effects), indirect genetic effects (for example, effects of alleles in parents on offspring through the environment) and bias from confounding. Within-family genetic variation is random, enabling unbiased estimation of direct genetic effects when parents are genotyped. However, parental genotypes are often missing. We introduce a method that imputes missing parental genotypes and estimates direct genetic effects. Our method, implemented in the software package snipar (single-nucleotide imputation of parents), gives more precise estimates of direct genetic effects than existing approaches. Using 39,614 individuals from the UK Biobank with at least one genotyped sibling/parent, we estimate the correlation between direct genetic effects and effects from standard GWASs for nine phenotypes, including educational attainment (r = 0.739, standard error (s.e.) = 0.086) and cognitive ability (r = 0.490, s.e. = 0.086). Our results demonstrate substantial confounding bias in standard GWASs for some phenotypes. snipar is a software package for imputing missing parental genotypes and estimating direct genetic effects. Application to UK Biobank data shows that effects estimated by standard genome-wide association study designs have confounding bias for some phenotypes.
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基因发现和多基因预测，从基因组全基因组协会的教育程度研究中，有110万个人。
影响因子：
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30.8
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Price, Alkes L.