Abstract STUDY QUESTION Do expectant parents experience increased anxiety and depression during pregnancies conceived through ART compared to spontaneous conception? SUMMARY ANSWER Among all expectant parents in the sample, those who conceived through ART reported overall lower levels of anxiety and depression in pregnancy compared to expectant parents who conceived spontaneously, while in the subsample of parents who conceived both through ART and spontaneous conception, expectant mothers experienced increased anxiety and depression in early pregnancy following ART compared to spontaneous conception. WHAT IS KNOWN ALREADY Previous research on expectant parents’ psychosocial adjustment in response to ART has found mixed results, with some studies suggesting ART is associated with increased anxiety and depression, and other studies suggesting improved mental health or no relationship. Mixed findings may relate to the use of cross-sectional designs that do not account for confounding differences between groups, or variability in the timing of assessment. STUDY DESIGN, SIZE, DURATION This prospective cohort study used data from the Norwegian Mother, Father and Child Cohort Study (MoBa), which includes 2960 pregnant women who underwent ART and 108 183 women who conceived spontaneously. Of these, a subsample of expectant parents had two consecutive pregnancies with one pregnancy resulting from ART and one conceived spontaneously (n = 286 women, n = 211 partners). Women self-reported their composite symptoms of anxiety and depression at two timepoints during each pregnancy (gestational weeks 17 and 30). Their partners self-reported composite symptoms of anxiety and depression at 17 weeks gestation during each pregnancy. Couples reported their relationship satisfaction at 17 weeks gestation. MAIN RESULTS AND THE ROLE OF CHANGE Using a conventional full-cohort analysis we found that ART was associated with less total anxiety and depression and greater relationship satisfaction, compared to spontaneous conception among both women and men. However, in the subsample of parents who experienced both ART and spontaneous pregnancies, ART was associated with increased levels of maternal anxiety and depression at gestational age 17 weeks (M = 1.19), compared to spontaneous pregnancies (M = 1.15), 95% CI of the mean difference 0.006, 0.074. At 30 weeks gestation, anxiety and depression were similar across both types of pregnancies. Expectant fathers reported similar levels of anxiety and depression at 17 weeks gestation during both pregnancies. Among women relationship satisfaction was higher following ART conception than spontaneous conception. LIMITATIONS, REASONS FOR CAUTION There is potential for selection effects in the sample, as women who have conceived through both ART and spontaneous conception in their first two pregnancies are rare. In addition, several factors that may be important predictors of mental health in this context, such as previous miscarriages and long-term infertility, were not assessed in the current study. WIDER IMPLICATIONS OF THE FINDINGS Our findings indicate that previous discrepancies in the literature may be related to inherent differences between the groups of parents receiving reproductive treatment and those who do not. This study addresses that limitation by prospectively comparing different types of pregnancies within the same expectant parents. Earlier inconsistencies may also relate to variations in gestational age when anxiety and depression were assessed. By examining symptoms at two timepoints in each pregnancy, we were able to examine the relation between gestational age and symptoms of anxiety and depression. STUDY FUNDING/COMPETING INTEREST(S) The MoBa is supported by the Norwegian Ministry of Health and the Norwegian Research Council/FUGE (grant number 151918/S10). This work was also supported by the Research Council of Norway grant number 288083 and 301004. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.

Abstract Body Genome-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. Disclosure No significant relationships.

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.