Communications Biology (Feb 2024)

Disentangling the link between maternal influences on birth weight and disease risk in 36,211 genotyped mother–child pairs

  • Jaakko T. Leinonen,
  • FinnGen,
  • Matti Pirinen,
  • Taru Tukiainen

DOI
https://doi.org/10.1038/s42003-024-05872-9
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 9

Abstract

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Abstract 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.