Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
Department of Public Health, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Commun Biol. 2024 Feb 12;7(1):175. doi: 10.1038/s42003-024-05872-9.
Epidemiological studies have robustly linked lower birth weight to later-life disease risks. These observations may reflect the adverse impact of intrauterine growth restriction on a child's health. However, causal evidence supporting such a mechanism in humans is largely lacking. Using Mendelian Randomization and 36,211 genotyped mother-child pairs from the FinnGen study, we assessed the relationship between intrauterine growth and five common health outcomes (coronary heart disease (CHD), hypertension, statin use, type 2 diabetes and cancer). We proxied intrauterine growth with polygenic scores for maternal effects on birth weight and took into account the transmission of genetic variants between a mother and a child in the analyses. We find limited evidence for contribution of normal variation in maternally influenced intrauterine growth on later-life disease. Instead, we find support for genetic pleiotropy in the fetal genome linking birth weight to CHD and hypertension. Our study illustrates the opportunities that data from genotyped parent-child pairs from a population-based biobank provides for addressing causality of maternal influences.
流行病学研究有力地将低出生体重与晚年疾病风险联系起来。这些观察结果可能反映了宫内生长受限对儿童健康的不利影响。然而，支持这种机制在人类中存在的因果证据在很大程度上是缺乏的。利用孟德尔随机化方法和来自芬兰基因研究的 36211 对基因分型的母婴对，我们评估了宫内生长与五种常见健康结果（冠心病 (CHD)、高血压、他汀类药物使用、2 型糖尿病和癌症）之间的关系。我们用多基因评分来代表母亲对出生体重的影响来代表宫内生长，并且在分析中考虑了母亲和孩子之间遗传变异的传递。我们发现，正常的、受母亲影响的宫内生长的变异对晚年疾病的影响的证据有限。相反，我们发现胎儿基因组中的遗传多效性支持将出生体重与 CHD 和高血压联系起来的因果关系。我们的研究说明了从基于人群的生物库中基因分型的亲子对中获得的数据为解决母亲影响的因果关系提供的机会。
