Fetal growth is an
indicator of fetal survival, regulated by maternal and fetal factors, but little is known about the underlying molecular mechanisms. We used Mendelian randomization to explore the effects of maternal and fetal genetically-instrumented
plasma proteins on
birth weight using genome-wide association summary data (n=406,063 with maternal and/or fetal genotype), with independent replication (n=74,932 mothers and n=62,108 offspring), and colocalisation. Higher genetically-predicted maternal levels of PCSK1 increased
birthweight (mean-difference: 9g (95% CI: 5g, 13g) per 1 standard deviation
protein level). Higher maternal levels of
LGALS4 decreased
birthweight (-54g (-29g, -80g)), as did VCAM1, RAD51D and GP1BA. In the offspring, higher genetically-predicted fetal levels of
LGALS4 (46g (23g, 70g)) increased
birthweight, alongside FCGR2B. Higher offspring levels of PCSK1 decreased
birth weight (-9g (-16g, 4g), alongside LEPR. Results support maternal and fetal
protein effects on
birth weight, implicating roles for
glucose metabolism, energy homeostasis, endothelial function and adipocyte differentiation.