Variants in calcium voltage-gated channel subunit Alpha1 C-gene (CACNA1C) are associated with sleep latency in infants

Genetic variants in CACNA1C (calcium voltage-gated channel subunit alpha1 C) are associated with bipolar disorder and schizophrenia where sleep disturbances are common. In an experimental model, Cacna1c has been found to modulate the electrophysiological architecture of sleep. There are strong genetic influences for consolidation of sleep in infancy, but only a few studies have thus far researched the genetic factors underlying the process. We hypothesized that genetic variants in CACNA1C affect the regulation of sleep in early development. Seven variants that were earlier associated (genome-wide significantly) with psychiatric disorders at CACNA1C were selected for analyses. The study sample consists of 1086 infants (520 girls and 566 boys) from the Finnish CHILD-SLEEP birth cohort (geno-typed by Illumina Infinium PsychArray BeadChip). Sleep length, latency, and nightly awakenings were reported by the parents of the infants with a home-delivered questionnaire at 8 months of age. The genetic influence of CACNA1C variants on sleep in infants was examined by using PLINK software. Three of the examined CACNA1C variants, rs4765913, rs4765914, and rs2239063, were associated with sleep latency (permuted PPeer reviewe

Association between Dopamine Receptor D2 (DRD2) Variations rs6277 and rs1800497 and Cognitive Performance According to Risk Type for Psychosis : A Nested Case Control Study in a Finnish Population Sample

Background There is limited research regarding the association between genes and cognitive intermediate phenotypes in those at risk for psychotic disorders. Methods We measured the association between established psychosis risk variants in dopamine D2 receptor (DRD2) and cognitive performance in individuals at age 23 years and explored if associations between cognition and these variants differed according to the presence of familial or clinical risk for psychosis. The subjects of the Oulu Brain and Mind Study were drawn from the general population-based Northern Finland 1986 Birth Cohort (NFBC 1986). Using linear regression, we compared the associations between cognitive performance and two candidate DRD2 polymorphisms (rs6277 and rs1800497) between subjects having familial (n=61) and clinical (n=45) risk for psychosis and a random sample of participating NFBC 1986 controls (n=74). Cognitive performance was evaluated using a comprehensive battery of tests at follow-up. Results Principal components factor analysis supported a three-factor model for cognitive measures. The minor allele of rs6277 was associated with poorer performance on a verbal factor (p=0.003) but this did not significantly interact with familial or clinical risk for psychosis. The minor allele of rs1800497 was associated with poorer performance on a psychomotor factor (p=0.038), though only in those at familial risk for psychotic disorders (interaction p=0.049). Conclusion The effect of two DRD2 SNPs on cognitive performance may differ according to risk type for psychosis, suggesting that cognitive intermediate phenotypes differ according to the type (familial or clinical) risk for psychosis.Peer reviewe

Interaction between compound genetic risk for schizophrenia and high birth weight contributes to social anhedonia and schizophrenia in women

Schizophrenia is a highly heritable disease, but despite extensive study, its genetic background remains unresolved. The lack of environmental measures in genetic studies may offer some explanation. In recent Finnish studies, high birth weight was found to increase the risk for familial schizophrenia. We examined the interaction between a polygenic risk score for schizophrenia and high birth weight on social anhedonia and schizophrenia in a general population birth cohort. The study sample included 4223 participants from the 1966 Northern Finland Birth Cohort. As a replication sample we used 256 participants from a systematically collected sample of Finnish schizophrenia families. The polygenic risk score comprised of variants published in the large genome-wide meta analysis for schizophrenia. We found the association between the polygenic risk score and social anhedonia stronger among those with high birth weight, and the same phenomenon was seen for schizophrenia among women, suggesting a gene-environment interaction. Similar results were found within the replication sample. Our results suggest a role for gene-environment interactions in assessing the risk of schizophrenia. Failure to take environmental effects into account may be one of the reasons why identifying significant SNPs for schizophrenia in genome-wide studies has been challenging.Peer reviewe

Polygenic risk for neuroticism is associated with externalizing symptoms in 2-year-old boys

Funding Information: The study was supported by the Academy of Finland (#308589 and #325292/Profi 5 LK; #308588 and #342747 EJP; #134880 and #253346 TP), Finnish State Grants for Clinical Research (ERVA) (LK) , Signe and Ane Gyllenberg Foundation (LK and TP). Publisher Copyright: © 2023 The AuthorsRecent advances in genome-wide association studies have enabled the estimation of genetic risk of complex traits, including neuroticism, with polygenic risk scores (PRS). Neuroticism PRS has been associated with psychiatric disorders and symptoms in adults, but studies in children are scarce. We studied whether neuroticism PRS, and its subscales, worry PRS and depressive affect PRS, were associated with externalizing and internalizing symptoms in 2-year-olds. We also examined parental neuroticism PRSs' association with children's externalizing and internalizing symptoms and whether parental depressive symptoms mediated the effect. Participants from two Finnish birth cohorts, CHILD-SLEEP and FinnBrain Birth Cohort Study, who had DNA and data on Brief Infant-Toddler Social and Emotional Assessment (BITSEA) available were included in the study (N = 806 and N = 987, respectively). PRSs were calculated based on GWAS data from UK Biobank. Child's neuroticism PRS, and its subscale worry PRS, were positively associated with externalizing symptoms in 2-year-old boys, but not in girls. Mother's depressive symptoms mediated the association between maternal neuroticism PRS and externalizing and internalizing symptoms in boys, but not in girls. Our results suggest that neuroticism PRS, and its subscale worry PRS, are associated with externalizing symptoms in already as young as 2-year-old boys, and, that subclinical symptoms of maternal depression that are based on genetic disposition, have an effect on boy's internalizing and externalizing symptoms. As we did not find any associations in girls, our study supports the suggestion that girls and boys may differ in how genetic and environmental factors contribute to their development.Peer reviewe