Smoking is a major risk factor for several somatic diseases, and is also emerging as a causal factor for neuropsychiatric disorders. Genome-wide association (GWA) and candidate gene studies for smoking behavior and nicotine dependence (ND) have disclosed too few predisposing variants to account for the high estimated heritability. Prior large-scale GWA studies have had very limited phenotypic definitions of relevance to smoking-related behavior, which has likely impeded the discovery of genetic effects. We performed genome-wide association analyses on 1114 adult twins ascertained for ever smoking from the population-based Finnish Twin Cohort study. The availability of 17 smoking-related phenotypes allowed us to comprehensively portray the dimensions of smoking behavior, clustered into the domains of smoking initiation, amount smoked, and ND. Our results highlight a locus on 16p12.3, with several SNPs in the vicinity of CLEC19A showing association (P<1×10−6) with smoking quantity. Interestingly, CLEC19A is located close to a previously reported attention deficit hyperactivity disorder (ADHD) linkage locus and an evident link between ADHD and smoking has been established. Intriguing preliminary association (P<1×10−5) was detected between DSM-IV ND diagnosis and several SNPs in ERBB4, coding for a Neuregulin receptor, on 2q33. The association between ERBB4 and DSM-IV ND diagnosis was replicated in an independent Australian sample. Interestingly, in the paper by Turner et al., significant increase in ErbB4 and Neuregulin 3 (Nrg3) expression was revealed following chronic nicotine exposure and withdrawal in mice. Turner et al. also detected an association between NRG3 SNPs and smoking cessation success in a clinical trial. ERBB4 has previously been associated with schizophrenia; further, it is located within an established schizophrenia linkage locus and within a linkage locus for a smoker phenotype identified in this sample. As a conclusion, we disclose novel tentative evidence for the involvement of ERBB4 in ND, suggesting the involvement of the Neuregulin/ErbB signalling pathway in addictions and providing a plausible link between the high co-morbidity of schizophrenia and ND.
We demonstrate novel associations of DSM-IV ND symptoms and the NDSS tolerance subscale. Our results confirm and extend association findings for other ND measures. We show pleiotropic effects of this gene cluster on multiple measures of ND and also regular drinking and the comorbidity of ND and depression.
This article describes how the policy to emphasize noninstitutional care is reflected in home care service strategies and work characteristics as well as the work motivation of home care staff in Finland. The data were gathered through a questionnaire answered by 312 employees in home care services and 22 social welfare and primary health care administrators. The methods of analysis used were cross-tabulations, one-way analysis of variance, and regression analysis. According to the results, institutional care had been reduced too fast and home care services had not been developed sufficiently. Most of the staff reported that their work had changed considerably. Although their work had become more interesting and more independent, over one third of the employees felt that the pressure of work had become unbearable and their responsibility was too heavy. The views of the home care staff differed from those of the administrators regarding the change strategies that had been carried out. The majority of the staff were moderately or highly motivated. Thirty-four percent of the variance of work motivation was explained mainly by work characteristics. More attention should be paid to the development of home care services before institutional care is reduced. Training the staff and informing them about the planned reform should not be neglected.
BackgroundThe aims of this study were to analyze associations of dopamine receptor genes (DRD1-5) with Major Depressive Disorder (MDD) and nicotine dependence (ND), and to investigate whether ND moderates genetic influences on MDD.MethodsThe sample was ascertained from the Finnish Twin Cohort. Twin pairs concordant for smoking history were recruited along with their family members, as part of the multisite Nicotine Addiction Genetics consortium. Genetic association analyses were based on 1428 adults. Total of 70 tagging single nucleotide polymorphisms within the dopamine receptor genes were genotyped and analyzed for association with MDD, ND, and MD-ND co-morbidity. Individual level logistic regression analyses were based on 1296 adults with data on ND and MDD diagnoses, as well as on dopamine receptor genotypes adjusted for sex, age, and alcohol use. Four independent samples, such as population-based and case-control samples, were used for replication.ResultsRs2399496, located 1.5 kb downstream of DRD3, showed suggestive association for MDD (p = 0.00076) and significant association for MDD-ND co-morbidity (p = 0.000079). Suggestive gene-(rs2399496) by-ND-interaction justified analyses by genetic risk variant and ND status. Individuals with ND and two minor alleles (AA) of rs2399496 had almost six-fold risk for MDD (OR 5.74, 95%CI 3.12–10.5, p = 9.010e-09) compared to individuals without ND and with two major alleles (TT).ConclusionsSignificant association between a variant downstream of DRD3 and a co-morbid MDD-ND phenotype was detected. Our results further suggest that nicotine dependence may potentiate the influence of the DRD3 genetic variant on MDD.
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