Fig. 1: Four credible ways in which maternal single nucleotide polymorphism (SNP)s can be related to offspring birthweight and offspring cardiometabolic risk factors.

a Maternal SNPs produce an adverse in utero environment that leads to fetal growth restriction and subsequently low offspring birthweight and developmental compensations that produce increased risk of offspring cardiometabolic disease in later life. b Maternal SNPs produce an adverse in utero environment that leads to fetal growth restriction and low offspring birthweight. Low offspring birthweight in turn is causal for increased risk of offspring cardiometabolic disease. c Maternal SNPs produce an adverse in utero environment that leads to fetal growth restriction and reduced birthweight. The same SNPs are transmitted to the offspring and pleiotropically influence offspring cardiometabolic risk through the offspring genome. d Maternal SNPs produce an adverse in utero environment that leads to fetal growth restriction and reduced offspring birthweight. SNPs that exert maternal effects on offspring birthweight also pleiotropically influence offspring cardiometabolic disease through the postnatal environment. The star on the arrows denotes the act of conditioning on maternal or offspring genotype blocking the association between maternal and offspring variables. The dotted paths indicate paths in which the maternal genotype can be related to offspring phenotype that are not to do with intrauterine growth restriction. Finally, we note that some offspring SNPs may also exert direct effects on offspring birthweight (these not shown). The presence of direct effects from offspring genotype on offspring birthweight is inconsequential so long as the relevant analyses are conditional on offspring genotype.