Fetal alleles predisposing to metabolically favourable adiposity are associated with higher birth weight

Abstract

BACKGROUND: Higher birthweight is associated with higher adult BMI. Alleles that predispose to greater adult adiposity might act in fetal life to increase fetal growth and birthweight. Whether there are fetal effects of recently identified adult metabolically favourable adiposity alleles on birthweight is unknown. Aim We aimed to test the effect on birthweight of fetal genetic predisposition to higher metabolically favourable adult adiposity and compare that with the effect of fetal genetic predisposition to higher adult BMI. METHODS: We used published GWAS data (n = upto 406 063) to estimate fetal effects on birthweight (adjusting for maternal genotype) of alleles known to raise metabolically favourable adult adiposity or BMI. We combined summary data across SNPs with random effects meta-analyses. We performed weighted linear regression of SNP-birthweight effects against SNP-adult adiposity effects to test for a dose-dependent association. RESULTS: Fetal genetic predisposition to higher metabolically favourable adult adiposity and higher adult BMI were both associated with higher birthweight (3grams per effect allele (95%CI, 1 to 5) averaged over 14 SNPs; p = 0.002; 0.5grams per effect allele (95%CI, 0 to 1) averaged over 76 SNPs; p = 0.042, respectively). SNPs with greater effects on metabolically favourable adiposity tended to have greater effects on birthweight (R2 = 0.2912, p = 0.027). There was no dose-dependent association for BMI (R2 = -0.0019, p = 0.602). CONCLUSIONS: Fetal genetic predisposition to both higher adult metabolically favourable adiposity and BMI is associated with birthweight. Fetal effects of metabolically favourable adiposity-raising alleles on birthweight are modestly proportional to their effects on future adiposity, but those of BMI-raising alleles are not.