Disentangling direct and indirect genetic effects from partners and offspring on maternal depression using trio-GCTA

Ludvig Daae Bjørndal, Espen Moen Eilertsen, Ziada Ayorech, Rosa Cheesman, Yasmin I. Ahmadzadeh, Jessie R. Baldwin, Helga Ask, Laurie John Hannigan, Tom A. McAdams, Alexandra Havdahl, Ragnhild Bang Nes, Espen Røysamb, Eivind Ystrom
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Abstract

Maternal depressive symptoms are highly prevalent and can negatively impact affected individuals and family members. Understanding etiological influences on maternal depression, such as genetic liability, is key to inform treatment and prevention efforts. Here we quantified direct and indirect genetic effects (that is, when genetic variants in other individuals influence risk of maternal depression through the environment) from partners and offspring on maternal depressive symptoms at multiple time points using genome-wide complex trait analysis with parent–offspring trios. We used data from the Norwegian Mother, Father and Child cohort study, including up to 21,000 genotyped parent–offspring trios. Models with indirect genetic effects had best fit at three out of five time points (3, 5 and 8 years after birth). The variance in maternal depressive symptoms explained by direct genetic effects ranged from 5% to 14%, whereas indirect genetic effects explained 0–14% of variance across time points. Heritable traits in family members contribute to maternal depressive symptoms through the environment at several time points after birth. The authors used a large sample of trios from the MoBa cohort study to estimate direct and indirect genetic effects on maternal depression at various time points using trio-GCTA.

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利用三重遗传效应分析法(Trio-GCTA)区分伴侣和后代对母亲抑郁的直接和间接遗传效应
产妇抑郁症状非常普遍,会对受影响的个人和家庭成员造成负面影响。了解孕产妇抑郁症的病因影响(如遗传责任)是为治疗和预防工作提供信息的关键。在此,我们利用亲子三人组的全基因组复杂性状分析,量化了伴侣和后代在多个时间点对母亲抑郁症状的直接和间接遗传效应(即其他个体的遗传变异通过环境影响母亲抑郁症的风险)。我们使用了挪威母亲、父亲和孩子队列研究的数据,其中包括多达 21,000 个基因分型的父母-后代三人组。在五个时间点中的三个(出生后 3 年、5 年和 8 年),具有间接遗传效应的模型拟合效果最佳。由直接遗传效应解释的母亲抑郁症状的变异在5%到14%之间,而间接遗传效应在不同时间点解释的变异在0%到14%之间。家庭成员的遗传特征通过出生后几个时间点的环境对产妇抑郁症状产生了影响。作者利用 MoBa 队列研究中的大量三人样本,使用三人-GCTA 估测了不同时间点上母亲抑郁的直接和间接遗传效应。
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