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.

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.

Background Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common and most heritable childhood-onset neuropsychiatric disorders, characterized by multifaceted genetics. To date, genetic studies of ADHD focused on additive effects only, explaining just a fraction of its heritability. Thus, we aimed at examining parent of origin effects (POE) together with maternal and additive effects, providing novel insight into the complex genetic architecture of ADHD. Methods We compiled parent-offspring data collected through the Psychiatric Genomics Consortium and the Norwegian Mother and Child Cohort, consisting of 2060 trios and 328 duos. Additional parent-offspring data is being added. ADHD was diagnosed based on DSM-IV, ICD-10 and child behavior checklist. POE, maternal and additive genetic effects are being evaluated using multinomial modelling implemented in EMIM software. We explored our signals in the light of known imprinted genes (POE) and the largest ADHD Genome-Wide Association Study (GWAS) in children (N=17666). Gene based analyses are being performed using MAGMA software. Heritability estimates and genetic correlations of the examined effects are being calculated using LD score regression. Results Our preliminary results indicate the presence of non-additive genetic effects in the development of ADHD. Our preliminary strongest imprinting signal is located in CALD1 locus (rs11980823, effect=0.77, SE=0.14, P=1.21E-07). This gene also revealed strong association signal in the previously reported large-scale childhood ADHD GWAS (rs79846815, P=2.03E-06). CALD1 plays essential an role in nerve regeneration, a function previously implicated in a number of neuropsychiatric disorders. Our preliminary gene-based analyses of the known imprinted genes revealed strong association with TP73 locus (P=0.0034), encoding a transcription factor implicated in disorders of nervous system (e.g. neuroblastoma). Additional hits were noted in the non-coding RNA genes, adding to the recent observations in neuropsychiatric genetics of gene regulation playing a pivotal role in the development of disorders of mental health. Discussion In conclusion, this is the first and the largest genome-wide parent-offspring study in ADHD, exploring its non-additive genetic effects by detecting and distinguishing between POE (imprinting), maternal and child effects. As we increase our sample size, we will provide estimates of such effects as well as those of their heritability and genetic correlations.

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.