Lack of association of the 5-HT(3A) receptor with schizophrenia.

The serotonin type 3 (5-HT(3) ) receptor (R) belongs to the family of ligand-gated ion channels. It is supposed to play an important role in the pathogenesis of schizophrenia and might also represent an interesting target for the pharmacological treatment of this disorder. In this study, we searched for variations within the 5-HT(3A) receptor gene which might be specifically associated to schizophrenia. Twenty-nine single nucleotide polymorphisms (SNPs) of 943 schizophrenic patients compared to 2,343 healthy individuals were analyzed. SNPs were selected taking into account previous results on a 5-HT(3A) receptor domain involved in neuroleptic binding. Dominant logistic and linear regression models were calculated for the phenotypes number of hospitalizations, duration of hospitalization, age at onset and case-control. The data did not show significant associations of any SNP under investigation specific for schizophrenic patients. In conclusion, our study does not support the hypothesis that the 5-HT(3A) receptor plays a major role in the pathogenesis of schizophrenia.

Genome-wide association uncovers shared genetic effects among personality traits and mood states.

Measures of personality and psychological distress are correlated and exhibit genetic covariance. We conducted univariate genome-wide SNP (~2.5 million) and gene-based association analyses of these traits and examined the overlap in results across traits, including a prediction analysis of mood states using genetic polygenic scores for personality. Measures of neuroticism, extraversion, and symptoms of anxiety, depression, and general psychological distress were collected in eight European cohorts (n ranged 546-1,338; maximum total n = 6,268) whose mean age ranged from 55 to 79 years. Meta-analysis of the cohort results was performed, with follow-up associations of the top SNPs and genes investigated in independent cohorts (n = 527-6,032). Suggestive association (P = 8 × 10(-8)) of rs1079196 in the FHIT gene was observed with symptoms of anxiety. Other notable associations (P < 6.09 × 10(-6)) included SNPs in five genes for neuroticism (LCE3C, POLR3A, LMAN1L, ULK3, SCAMP2), KIAA0802 for extraversion, and NOS1 for general psychological distress. An association between symptoms of depression and rs7582472 (near to MGAT5 and NCKAP5) was replicated in two independent samples, but other replication findings were less consistent. Gene-based tests identified a significant locus on chromosome 15 (spanning five genes) associated with neuroticism which replicated (P < 0.05) in an independent cohort. Support for common genetic effects among personality and mood (particularly neuroticism and depressive symptoms) was found in terms of SNP association overlap and polygenic score prediction. The variance explained by individual SNPs was very small (up to 1%) confirming that there are no moderate/large effects of common SNPs on personality and related traits.