Testing the role of circadian genes in conferring risk for psychiatric disorders

Disturbed sleep and disrupted circadian rhythms are a common feature of psychiatric disorders, and many groups have postulated an association between genetic variants in circadian clock genes and psychiatric disorders. Using summary data from the association analyses of the Psychiatric Genomics Consortia (PGC) for schizophrenia, bipolar disorder and major depressive disorder, we evaluated the evidence that common SNPs in genes encoding components of the molecular clock influence risk to psychiatric disorders. Initially, gene-based and SNP P-values were analyzed for 21 core circadian genes. Subsequently, an expanded list of genes linked to control of circadian rhythms was analyzed. After correcting for multiple comparisons, none of the circadian genes were significantly associated with any of the three disorders. Several genes previously implicated in the etiology of psychiatric disorders harbored no SNPs significant at the nominal level of

Role of Nicotine Dependence in the Association between the Dopamine Receptor Gene DRD3 and Major Depressive Disorder

Peer reviewe

Meta-analysis of genome-wide association studies of anxiety disorders.

Anxiety disorders (ADs), namely generalized AD, panic disorder and phobias, are common, etiologically complex conditions with a partially genetic basis. Despite differing on diagnostic definitions based on clinical presentation, ADs likely represent various expressions of an underlying common diathesis of abnormal regulation of basic threat-response systems. We conducted genome-wide association analyses in nine samples of European ancestry from seven large, independent studies. To identify genetic variants contributing to genetic susceptibility shared across interview-generated DSM-based ADs, we applied two phenotypic approaches: (1) comparisons between categorical AD cases and supernormal controls, and (2) quantitative phenotypic factor scores (FS) derived from a multivariate analysis combining information across the clinical phenotypes. We used logistic and linear regression, respectively, to analyze the association between these phenotypes and genome-wide single nucleotide polymorphisms. Meta-analysis for each phenotype combined results across the nine samples for over 18 000 unrelated individuals. Each meta-analysis identified a different genome-wide significant region, with the following markers showing the strongest association: for case-control contrasts, rs1709393 located in an uncharacterized non-coding RNA locus on chromosomal band 3q12.3 (P=1.65 × 10(-8)); for FS, rs1067327 within CAMKMT encoding the calmodulin-lysine N-methyltransferase on chromosomal band 2p21 (P=2.86 × 10(-9)). Independent replication and further exploration of these findings are needed to more fully understand the role of these variants in risk and expression of ADs.Molecular Psychiatry advance online publication, 12 January 2016; doi:10.1038/mp.2015.197

The association between workplace smoking bans and self-perceived, work-related stress among smoking workers

<p>Abstract</p> <p>Background</p> <p>There is substantial empirical evidence on the benefits of smoking bans; however, the unintended consequences of this anti-smoking measure have received little attention. This paper examines whether workplace smoking bans (WSB's) are associated with higher self-perceived, work-related stress among smoking workers.</p> <p>Methods</p> <p>A longitudinal representative sample of 3,237 individuals from the Canadian National Population Health Survey from 2000 to 2008 is used. Work-related stress is derived from a 12-item job questionnaire. Two categories of WSB's, full and partial, are included in the analysis, with no ban being the reference category. Analysis also controls for individual socio-demographic characteristics, health status, provincial and occupational fixed-effects. We use fixed-effects linear regression to control for individual time-invariant confounders, both measured and unmeasured, which can affect the relationship between WSB's and work-related stress. To examine the heterogeneous effects of WSB's, the analysis is stratified by gender and age. We check the robustness of our results by re-estimating the baseline specification with the addition of different control variables and a separate analysis for non-smokers.</p> <p>Results</p> <p>Multivariate analysis reveals a positive and statistically significant association between full <it>(β = 0.75, CI = 0.19-1.32) </it>or partial <it>(β = 0.69, CI = 0.12-1.26) </it>WSB's, and the level of self-perceived, work-related stress among smoking workers compared to those with no WSB. We also find that this association varies by gender and age. In particular, WSB's are significantly associated with higher work stress only for males and young adults (aged 18-40). No statistically significant association is found between WSB's and the level of self-perceived work-related stress among non-smoking workers.</p> <p>Conclusion</p> <p>The results of this study do not imply that WSB's are the main determinant of self-perceived, work-related stress among smokers but provides suggestive evidence that these may be positively related.</p

Does smoking among friends explain apparent genetic effects on current smoking in adolescence and young adulthood?

We used data from a prospective cohort study of twins to investigate the influence of unmeasured genetic and measured and unmeasured environmental factors on the smoking behaviour of adolescents and young adults. Twins were surveyed in 1988 (aged 11–18 years), 1991, 1996 and 2004 with data from 1409, 1121, 732 and 758 pairs analysed from each survey wave, respectively. Questionnaires assessed the smoking behaviour of twins and the perceived smoking behaviour of friends and parents. Using a novel logistic regression analysis, we simultaneously modelled individual risk and excess concordance for current smoking as a function of zygosity, survey wave, parental smoking and peer smoking. Being concordant for having peers who smoked was a predictor of concordance for current smoking (P<0.001). After adjusting for peer smoking, monozygotic (MZ) pairs were no more alike than dizygotic pairs for current smoking at waves 2, 3 and 4. Genetic explanations are not needed to explain the greater concordance for current smoking among adult MZ pairs. However, if they are invoked, the role of genes may be due to indirect effects acting through the social environment. Smoking prevention efforts may benefit more by targeting social factors than attempting to identify genetic factors associated with smoking