Replication of a genome-wide association study of birth weight in preterm neonates.

Objective To examine associations between rs9883204 in ADCY5 and rs900400 near LEKR1 and CCNL1 with birth weight in a preterm population. Both markers were associated with birth weight in a term population in a recent genome-wide association study of Freathy et al. Study design A meta-analysis of mother and infant samples was performed for associations of rs900400 and rs9883204 with birth weight in 393 families from the US, 265 families from Argentina, and 735 mother-infant pairs from Denmark. Z-scores adjusted for infant sex and gestational age were generated for each population separately and regressed on allele counts. Association evidence was combined across sites by inverse-variance weighted meta-analysis. Results Each additional C allele of rs900400 (LEKR1/CCNL1) in infants was marginally associated with a 0.069 SD lower birth weight (95% CI, -0.159 to 0.022; P=.068). This result was slightly more pronounced after adjusting for smoking (P=.036). No significant associations were identified with rs9883204 or in maternal samples. Conclusions These results indicate the potential importance of this marker on birth weight regardless of gestational age. (J Pediatr 2012;160:19-24).