Elucidating the role of maternal environmental exposures on offspring health and disease using two-sample Mendelian randomization
Elucidating the role of maternal environmental exposures on offspring health and disease using two-sample Mendelian randomization
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DOI：
10.1093/ije/dyz019
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发表时间：
2019-06-01
影响因子：
7.7
通讯作者：
Warrington, Nicole M.
中科院分区：
文献类型：
--
作者：
Evans, David M.;Moen, Gunn-Helen;Warrington, Nicole M.
背景：人们对评估一系列孕产妇环境暴露对后代健康相关结果的因果影响非常感兴趣。以前使用孟德尔随机化方法进行的尝试因缺乏具有大量基因分型母子对的流行病学队列而受到阻碍。方法：我们描述了我们创建的一种新的统计模型，该模型可用于估计母体基因型对后代结果的影响（以后代基因型为条件），使用个体水平和汇总结果数据，甚至 当样本重叠程度未知时。结果：我们描述了如何将从我们的方法获得的估计值随后用于大规模双样本孟德尔随机化研究，以调查母亲环境暴露对后代结果的因果影响。这包括旨在评估与胎儿生长受限相关的子宫内暴露对后代未来疾病风险的因果影响的研究。我们使用与后代出生体重和心脏代谢疾病相关的例子来说明我们的框架，尽管我们拥护的一般原则与许多其他后代表型相关。结论：我们主张建立大规模的国际遗传学联盟，专注于识别母体遗传效应，并致力于公开共享此类努力的全基因组总结结果数据。这些信息将有助于对母亲暴露和后代结果进行强有力的两样本孟德尔随机化研究的应用。
Background: There is considerable interest in estimating the causal effect of a range of maternal environmental exposures on offspring health-related outcomes. Previous attempts to do this using Mendelian randomization methodologies have been hampered by the paucity of epidemiological cohorts with large numbers of genotyped mother-offspring pairs.Methods: We describe a new statistical model that we have created which can be used to estimate the effect of maternal genotypes on offspring outcomes conditional on offspring genotype, using both individual-level and summary-results data, even when the extent of sample overlap is unknown.Results: We describe how the estimates obtained from our method can subsequently be used in large-scale two-sample Mendelian randomization studies to investigate the causal effect of maternal environmental exposures on offspring outcomes. This includes studies that aim to assess the causal effect of in utero exposures related to fetal growth restriction on future risk of disease in offspring. We illustrate our framework using examples related to offspring birthweight and cardiometabolic disease, although the general principles we espouse are relevant for many other offspring phenotypes.Conclusions: We advocate for the establishment of large-scale international genetics consortia that are focused on the identification of maternal genetic effects and committed to the public sharing of genome-wide summary-results data from such efforts. This information will facilitate the application of powerful two-sample Mendelian randomization studies of maternal exposures and offspring outcomes.