Association of Maternal Neurodevelopmental Risk Alleles With Early-Life Exposures
Association of Maternal Neurodevelopmental Risk Alleles With Early-Life Exposures
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DOI：
10.1001/jamapsychiatry.2019.0774
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发表时间：
2019-08-01
期刊：
影响因子：
25.8
通讯作者：
Stergiakouli, Evie
中科院分区：
文献类型：
--
作者：
Leppert, Beate;Havdahl, Alexandra;Stergiakouli, Evie
要点问题母亲神经发育障碍的多基因风险评分是否与生命早期暴露相关？研究结果在这项针对 7921 名母亲的基于人群的队列研究中，注意力缺陷/多动障碍的多基因风险评分与一系列与后代神经发育障碍相关的早期暴露相关。自闭症谱系障碍和精神分裂症的多基因风险评分显示，几乎没有证据表明与生命早期暴露相关。意义：研究结果表明，患有注意力缺陷/多动症的高遗传风险的母亲也可能面临某些不良妊娠暴露的风险增加，未来的研究应该对不同因果信息方法的证据进行三角测量。这项基于人群的队列研究评估了母亲神经发育障碍的多基因风险评分是否与先前与具有可用基因型的女性的疾病相关的早期生命暴露有关。 数据的重要性长期以来，生命早期的暴露，例如产前母亲的生活方式、疾病、营养缺乏、毒素水平和不良出生事件，一直被认为是后代神经发育障碍的潜在危险因素。然而，母体遗传因素可能会混淆早期暴露与后代神经发育结果之间的关联，这使得推断因果关系存在问题。目的测试母亲神经发育障碍多基因风险评分（PRS）是否与先前与该疾病相关的早期生命暴露相关。设计、设置和参与者在这项基于英国人口的队列研究中，7921 名拥有来自雅芳父母和儿童纵向研究 (ALSPAC) 基因型数据的母亲接受了母亲 PRS 与注意力缺陷/多动障碍 (ADHD PRS)、自闭症谱系障碍 (ASD PRS) 和精神分裂症 (SCZ PRS) 之间的关联测试，并有 32 次生命早期暴露。 ALSPAC 数据收集于 1990 年 9 月 6 日开始，目前仍在进行中。本研究的数据分析时间为 2018 年 4 月 1 日至 9 月 1 日。暴露母亲 ADHD PRS、ASD PRS 和 SCZ PRS 是使用来自最大的可用全基因组关联研究的发现效应大小估计值和 P 的显着性阈值来计算的。
Key PointsQuestionAre maternal polygenic risk scores for neurodevelopmental disorders associated with early-life exposures? FindingsIn this population-based cohort study of 7921 mothers, polygenic risk score for attention-deficit/hyperactivity disorder was associated with a range of early-life exposures linked to neurodevelopmental disorders in offspring. Polygenic risk scores for autism spectrum disorder and schizophrenia showed little evidence association with of early-life exposures. MeaningThe findings suggest that mothers at high genetic risk for attention-deficit/hyperactivity disorder may also be at increased risk for some adverse pregnancy exposures, and future studies should triangulate evidence from different causally informative approaches.This population-based cohort study assesses whether maternal polygenic risk scores for neurodevelopmental disorders are associated with early-life exposures previously linked to the disorders in women with available genotype data.ImportanceEarly-life exposures, such as prenatal maternal lifestyle, illnesses, nutritional deficiencies, toxin levels, and adverse birth events, have long been considered potential risk factors for neurodevelopmental disorders in offspring. However, maternal genetic factors could be confounding the association between early-life exposures and neurodevelopmental outcomes in offspring, which makes inferring a causal relationship problematic. ObjectiveTo test whether maternal polygenic risk scores (PRSs) for neurodevelopmental disorders were associated with early-life exposures previously linked to the disorders. Design, Setting, and ParticipantsIn this UK population-based cohort study, 7921 mothers with genotype data from the Avon Longitudinal Study of Parents and Children (ALSPAC) underwent testing for association of maternal PRS for attention-deficit/hyperactivity disorder (ADHD PRS), autism spectrum disorder (ASD PRS), and schizophrenia (SCZ PRS) with 32 early-life exposures. ALSPAC data collection began September 6, 1990, and is ongoing. Data were analyzed for the current study from April 1 to September 1, 2018. ExposuresMaternal ADHD PRS, ASD PRS, and SCZ PRS were calculated using discovery effect size estimates from the largest available genome-wide association study and a significance threshold of P