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

• Main Authors: Leinonen, Jaakko T., Pirinen, Matti, Tukiainen, Taru
• Other Authors: Genomics of Sex Differences, Institute for Molecular Medicine Finland, Helsinki Institute of Life Science HiLIFE, Centre of Excellence in Complex Disease Genetics, Helsinki Institute for Information Technology, Statistical and population genetics, Department of Mathematics and Statistics, Department of Public Health, Molecular and Integrative Biosciences Research Programme
• Format: Article in Journal/Newspaper
• Language: English
• Published: Springer 2024
• Subjects: Gynaecology and paediatrics; Coronary-heart-disease; Mendelian randomization; Fetal origins; Association; Inference; Born; Life; Arctic
• Online Access: http://hdl.handle.net/10138/572183

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.A Mendelian Randomization study with 36,211 mother-child pairs indicates that maternal genetic variants, influencing a child's birth weight, impact the child's risk for common diseases through inheritance and not by effects on intrauterine growth. Peer reviewed