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父母基因型的孟德尔插补改善了对直接遗传效应的估计
作者:小柯机器人 发布时间:2022/6/12 23:25:01

英国牛津大学的Augustine Kong和Alexander I. Young共同合作,近期取得重要工作进展,他们研究发现父母基因型的孟德尔插补改善了对直接遗传效应的估计。相关论文2022年6月9日在线出版于《自然—遗传学》杂志上。

在这里,研究人员介绍了一种估算缺失亲本基因型并估计直接遗传效应的方法。他们的方法在软件包snipar(父母的单核苷酸插补)中实现,与现有方法相比,可以更精确地估计直接遗传效应。利用来自英国生物库的39,614名至少有一个基因分型的兄弟姐妹/父母的个体,研究人员估计了直接遗传效应与标准GWASs对九种表型的影响之间的相关性,包括教育程度(r=0.739,标准误差(s.e.)=0.086)和认知能力(r=0.490,s.e.=0.086)。他们的结果表明,对于某些表型,标准GWASs存在显著的混杂偏差。

据介绍,全基因组关联研究(GWASs)估计的影响包括个体等位基因对该个体的影响(直接遗传效应),间接遗传影响(例如,父母等位基因通过环境对后代的影响)和混杂偏差。家族内遗传变异是随机的,当父母有基因型时,可以无偏差地估计直接的遗传效应。然而,亲本基因型经常缺失。

附:英文原文

Title: Mendelian imputation of parental genotypes improves estimates of direct genetic effects

Author: Young, Alexander I., Nehzati, Seyed Moeen, Benonisdottir, Stefania, Okbay, Aysu, Jayashankar, Hariharan, Lee, Chanwook, Cesarini, David, Benjamin, Daniel J., Turley, Patrick, Kong, Augustine

Issue&Volume: 2022-06-09

Abstract: 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.

DOI: 10.1038/s41588-022-01085-0

Source: https://www.nature.com/articles/s41588-022-01085-0

期刊信息

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:25.455
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex