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. 2018 Dec;8(12):e01144.
doi: 10.1002/brb3.1144. Epub 2018 Oct 31.

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

Dinka Smajlagić  1   2 , Kaya Kvarme Jacobsen  3 , Craig Myrum  3 , Jan Haavik  3 , Stefan Johansson  1   2 , Tetyana Zayats  3
Affiliations

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

Dinka Smajlagić et al. Brain Behav. 2018 Dec.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Avon Longitudinal Study of Parents and Children; glutamate; intelligence; mode of delivery.

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Figures

Figure 1
Figure 1
Regional plot of rs17800861. Variants are plotted by position on chromosome 16 against the observed interaction p‐values for FSIQ measure in the adjusted model. Local LD structure is reflected by estimated recombination rates from the HapMap CEU population (Utah residents with Northern and Western European ancestry plotted in red on the right side). The colors of the variants surrounding rs17800861 are reflecting their LD (according to pairwise r 2 values from the HapMap CEU population). “Genes” refers to protein‐coding genes in the presented region. “refGenes” refers to both protein‐coding and non‐protein‐coding genes reflecting the data from RefSeq UCSC tracks. “lincRNAsAllCellTypeTopView” reflects the data from the lncRNA UCSC tracks in brain tissue
Figure 2
Figure 2
Interaction plot reflecting a moderating effect of delivery mode on the correlation between FSIQ scores and rs17800861. The y‐axis represents the FSIQ scores, while the x‐axis displays rs17800861 genotypes. Error bars represent the standard error of the FSIQ scores
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