Recurrent copy number variations (CNVs) are common causes of neurodevelopmental disorders (NDDs) and associated with a range of psychiatric traits. These CNVs occur at defined genomic regions that are particularly prone to recurrent deletions and duplications and often exhibit variable expressivity and incomplete penetrance. Robust estimates of the population prevalence and inheritance pattern of recurrent CNVs associated with neurodevelopmental disorders (NDD CNVs) are lacking. Here we perform array-based CNV calling in 12,252 mother–father–child trios from the Norwegian Mother, Father, and Child Cohort Study (MoBa) and analyse the inheritance pattern of 26 recurrent NDD CNVs in 13 genomic regions. We estimate the total prevalence of recurrent NDD CNVs (duplications and deletions) in live-born children to 0.48% (95% C.I.: 0.37–0.62%), i.e., ~1 in 200 newborns has either a deletion or duplication in these NDDs associated regions. Approximately a third of the newborn recurrent NDD CNVs (34%, N = 20/59) are de novo variants. We provide prevalence estimates and inheritance information for each of the 26 NDD CNVs and find higher prevalence than previously reported for 1q21.1 deletions (~1:2000), 15q11.2 duplications (~1:4000), 15q13.3 microdeletions (~1:2500), 16p11.2 proximal microdeletions (~1:2000) and 17q12 deletions (~1:4000) and lower than previously reported prevalence for the 22q11.2 deletion (~1:12,000). In conclusion, our analysis of an unselected and representative population of newborns and their parents provides a clearer picture of the rate of recurrent microdeletions/duplications implicated in neurodevelopmental delay. These results will provide an important resource for genetic diagnostics and counseling.

IntroductionIntelligence 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.MethodsParticipants 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.ResultsA 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.ConclusionsOur 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.

BodyGenome-wide Association Studies in Psychiatry - Current Perspectives Last decade was exciting time for human genetic studies. Genome-wide association studies (GWASs), used to examine the association of genotyped variants across the entire genome and common complex phenotype(s), have led to many findings. Currently, GWAS Catalogue has collected 4,809 publications and 227,262 associated variants. In recent years, psychiatric genetics has enjoyed some success in discoveries of associated variants. This mostly happened because researchers were able to unite and generate large sample sets of patients and healthy controls in big consortia. As a result of large sample sizes becoming available for meta-GWASs, some of the first genome-wide significant loci in psychiatric and related neurodevelopmental traits were detected. However, most of the large-scale genetic studies are done primarily on European population and GWASs have huge diversity problem. Performing trans-ethnic GWASs on psychiatric traits can help us discover more associated variants. Another advantage of bringing many datasets together into large-scale meta-analyses is the ability to conduct cross-disorder studies. This is possible to be done on psychiatric traits since many of them share genetic liability. However, little research has been conducted on the genetic differences between related psychiatric traits. Identifying disorder-specific variants remain important open question. In this presentation we will bring an update of recent findings and current state of the art methods and analyses.DisclosureNo significant relationships.