Moderating effect of mode of delivery on the genetics of intelligence: Explorative genome-wide analyses in ALSPAC

Intelligence is a core construct of individual differences in cognitive abilities and a strong predictor of important life outcomes. Within recent years, rates of cesarean section have substantially increased globally, though little is known about its effect on neurodevelopmental trajectories. Thus, we aimed to investigate the influence of delivery by cesarean section on the genetics of intelligence in children.

Participants were recruited through the Avon Longitudinal Study of Parents and Children (ALSPAC). Intelligence was measured by the Wechsler Intelligence Scale for Children (WISC). Genotyping was performed using the Illumina Human Hap 550 quad genome-wide SNP genotyping platform and was followed by imputation using MACH software. Genome-wide interaction analyses were conducted using linear regression.

A total of 2,421 children and 2,141,747 SNPs were subjected to the genome-wide interaction analyses. No variant reached genome-wide significance. The strongest interaction was observed at rs17800861 in the GRIN2A gene (β = -3.43, 95% CI = -4.74 to -2.12, p = 2.98E-07). This variant is predicted to be located within active chromatin compartments in the hippocampus and may influence binding of the NF-kappaB transcription factor.

Our results may indicate that mode of delivery might have a moderating effect on genetic disposition of intelligence in children. Studies of considerable sizes (>10,000) are likely required to more robustly detect variants governing such interaction. In summary, the presented findings prompt the need for further studies aimed at increasing our understanding of effects various modes of delivery may have on health outcomes in children.