Genome-wide association study on detailed profiles of smoking behavior and nicotine dependence in a twin sample.

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.

Evening types are more often current smokers and nicotine-dependent-a study of Finnish adult twins.

AIMS: To examine the association between diurnal type and smoking status and nicotine dependence (ND). DESIGN: A cohort study using random-effects model regressions for repeated longitudinal panel data was used to analyse smoking status by diurnal type. Regression analyses examined the association between diurnal type and ND. PARTICIPANTS: A total of 23, 289 same-sex adult twin individuals from Finnish Twin Cohort. Nicotine dependence was studied in a subsample of 676 twin individuals. MEASUREMENTS: Subjects were classified by self-report into four categories: morning type, somewhat morning type, somewhat evening type, evening type (in 1981). Smoking status was defined as current and ever smoking (in 1975, 1981 and 1990). ND was measured by DSM-IV and Fagerström Test for Nicotine Dependence (FTND) (during 2001-05). Findings Evening types of both genders were much more likely to be current (OR = 2.91, 95% CI 2.50, 3.38) and life-time smokers (OR = 2.67, 95% CI 2.96, 4.07) compared to morning types. Evening types were less likely to stop smoking. The risk of nicotine dependence assessed by DSM-IV criteria was higher among evening types (OR = 2.78, 95% CI 1.64, 4.72). Evening types scored 0.59 (95% CI 0.01, 1.17) points higher than morning types on the FTND. Adjustment for potential confounders did not change these associations. CONCLUSIONS: Being an evening type is associated independently with a higher risk of being a current smoker, being more highly dependent upon cigarettes and a lower likelihood of stopping smoking. Understanding the cause of these associations could elucidate the causes of tobacco addiction.

Smoking strongly predicts disability retirement due to COPD: the Finnish Twin Cohort Study.

No previous studies on the association of smoking behaviour with disability retirement due to register verified chronic obstructive pulmonary disease (COPD) exist. This 30-yr follow-up study examined how strongly aspects of cigarette smoking predict disability retirement due to COPD. The study population consisted of 24,043 adult Finnish twins (49.7% females) followed from 1975 to 2004. At baseline the participants had responded to a questionnaire. Information on retirement was obtained from the Finnish pension registers. Smoking strongly predicted disability retirement due to COPD. In comparison to never-smokers, age adjusted hazard ratio (HR) for current smokers was 22.0 (95% CI 10.0-48.5) and for smokers with ≥ 12 pack-yrs was 27.3 (95% CI 12.6-59.5). Similar estimates of risk were observed in within-pair analyses of twin pairs discordant for disability retirement due to COPD. Among discordant monozygotic pairs those with disability pension due to COPD were more often current smokers. The effect of early smoking onset (< 18 yrs) on the risk of disability retirement due to COPD remained after adjustment for the amount smoked (HR 1.70, 95% CI 1.08-2.68). Smoking strongly predicts disability retirement due to COPD. Preventive measures against disability retirement and other harmful consequences of tobacco smoking should receive greater emphasis.

Bruxism is associated with nicotine dependence: a nationwide Finnish twin cohort study.

OBJECTIVES: To investigate the association of smoking with bruxism while controlling for genetic and environmental factors using a co-twin-control design. Especially, the role of nicotine dependence was studied in this context. METHODS: The material derives from the Finnish Twin Cohort consisting of 12,502 twin individuals who responded to a questionnaire in 1990 (response rate of 77%). All were born in 1930-1957, the mean age being 44 years. The questionnaire covered 103 multiple choice questions, 7 dealing with tobacco use and 22 with sleep and vigilance matters, including perceived bruxism. In addition, a subsample derived from the Nicotine Addiction Genetics Finland Study containing 445 twin individuals was studied. RESULTS: In age- and gender-controlled multinomial logistic regression, both monthly and rarely reported bruxism associated with both current cigarette smoking (odds ratio [OR] = 1.74 and 1.64) and former cigarette smoking (OR = 1.64 and 1.47). Weekly bruxism associated with current smoking (OR = 2.85). Current smokers smoking 20 or more cigarettes a day reported weekly bruxism more likely (OR = 1.61-1.97) than those smoking less. Among twin pairs (N = 142) in which one twin was a weekly bruxer and the cotwin a never bruxer, there were 13 monozygotic pairs in which one twin was a current smoker and the other twin was not. In all cases, the bruxer was the smoker (p = .0003). Nicotine dependence associated significantly with bruxism. CONCLUSIONS: Our twin study provides novel evidence for a possible causal link between tobacco use and bruxism among middle-aged adults. Nicotine dependence may be a significant predisposing factor for bruxism.

Linkage of nicotine dependence and smoking behavior on 10q, 7q and 11p in twins with homogeneous genetic background.

The significant worldwide health burden introduced by tobacco smoking highlights the importance of studying the genetic determinants of smoking behavior and the key factor sustaining compulsive smoking, that is, nicotine dependence (ND). We have here addressed the genetic background of smoking in a special study sample of twins, harmonized for early life events and specifically ascertained for smoking from the nationwide twin cohort of the genetically unique population of Finland. The twins and their families were carefully examined for extensive phenotype profiles and a genome-wide scan was performed to identify loci behind the smoking status, ND and the comorbid phenotype of ND and alcohol use in 505 individuals from 153 families. We replicated previous linkage findings on 10q (max logarithm of the odds (LOD) 3.12) for a smoker phenotype, and on 7q and 11p (max LOD 2.50, and 2.25, respectively) for the ND phenotype. The loci linked for ND also showed evidence for linkage for the comorbid phenotype. Our study provides confirmatory evidence for the involvement of these genome regions in the genetic etiology of smoking behavior and ND and for the first time associates drinking and smoking to a shared locus on 10q.

Changes in the work and motivation of staff delivering home care services in Finland.

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.