ABSTRACT
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. Previous 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 GWA 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 single-nucleotide polymorphisms (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 (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) 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. Recently, a significant increase in ErbB4 and Neuregulin 3 (Nrg3) expression was revealed following chronic nicotine exposure and withdrawal in mice and an association between NRG3 SNPs and smoking cessation success was detected 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. In 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.
Subject(s)
Drug-Seeking Behavior , Phenotype , Smoking/genetics , Smoking/psychology , Tobacco Use Disorder/genetics , Tobacco Use Disorder/psychology , Cohort Studies , Family , Female , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Linkage Disequilibrium , Male , Middle Aged , Receptor, ErbB-4/genetics , Twins, Dizygotic/genetics , Twins, Monozygotic/geneticsABSTRACT
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.
