New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

Rachel Freathy and colleagues report results of a large-scale genome-wide association study of birth weight. They identify four loci newly associated with this trait and find overlap between birth weight–associated loci and those influencing adult height and metabolism. Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood 1 . Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1 , with no obvious link to adult traits 2 . In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.