The genetics of low and high birthweight and their relationship with cardiometabolic disease – published online 05/04/25

Gunn-Helen Moen, Liang-Dar Hwang, Caroline Brito Nunes, Nicole M. Warrington, David M. Evans

Low and high birthweight infants are at increased risk of mortality and cardiometabolic complications in later life. In this issue, Moen et al (https://doi.org/10.1007/s00125-025-06420-8) report that low birthweight appeared to have a slightly different genetic aetiology to birthweight within the normal range. The authors performed a genome-wide association study of birthweight data in the UK Biobank including individuals with extremes of birthweight. Their analyses led to the discovery of 25 genetic loci for birthweight. They identified a low-frequency missense variant in the ABCC8 gene, a gene known to be involved in congenital hyperinsulinism, neonatal diabetes mellitus and MODY, that was estimated to be responsible for a massive 170 g increase in birthweight per allele. Individuals carrying this mutation were at substantially increased risk of high birthweight compared with normal pregnancies. The authors conclude that these results highlight the importance of genetic factors in the correlation between birthweight and cardiometabolic traits and diseases.

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