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

Abstract

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 to 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 to 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.

Neuronal Nitric Oxide Synthase (NOS1) Polymorphisms Interact with Financial Hardship to Affect Depression Risk

“…This study builds on previous reports associating NOS1 SNPs with current depression and psychological distress (McGuffin et al, 2005;Luciano et al, 2012) by demonstrating that the associations are likely to be mediated by responsivity to stress. The findings are compatible with findings in rodents implicating NOS1 in behavioural, neural, and endocrine responses to stress (Zhou et al, 2011).…”

“…SNPs in the NOS1 region (12q24) have been associated with major depression (McGuffin et al, 2005, Galecki et al, 2011 and with general psychological distress in a large multicentre GWA meta-analysis (Luciano et al, 2012). The present study tested the prediction that the influence of genetic variation in the NOS1 gene on current depression would be more apparent when tested in relation to recent/current adversity rather than in isolation.…”

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

“…A subsequent analysis of SNP heritability found significant genetic correlations between MDD and SCZ (0.43), BPD (0.47), and ADHD (0.37), respectively, supporting prior evidence from family and twin studies (Cross-Disorder Group of the Psychiatric Genomics Consortium et al, 2013). PRS analyses have also documented common variant overlap between MDD and anxiety symptoms as well as neuroticism Luciano et al, 2012;Middeldorp et al, 2011) and between PTSD and BPD (Nievergelt et al, 2015;Solovieff et al, 2014). In addition, pathway analyses by the PGC have revealed enrichment of multiple biological pathways across MDD, BPD, and SCZ (Network and Pathway Analysis Subgroup of Psychiatric Genomics Consortium, 2015).…”

Anxiety as a neurodevelopmental disorder in a neuronal subpopulation: Evidence from gene expression data

“…Thus, several genome wide association studies have picked up the gauntlet, trying to identify the candidate genes (Shifman et al, 2008;Calboli et al, 2010;Luciano et al, 2012;Otowa et al, 2012;Aragam et al, 2013).…”