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Introduction Low socio-economic status (SES) is strongly related to smoking, but studies examining the association of SES with nicotine dependence (ND) are scarce. The aim of this study was to examine the associations of SES and marital status with smoking, multiple measures of ND, and cotinine as a nicotine intake biomarker. Methods The sample comprised 1746 ever smokers, sampled from the National FINRISK 2007 Study, who had completed a tobacco specific questionnaire in addition to the standard clinical examination. The Fagerstrom Test for Nicotine Dependence (FTND), the Heaviness of Smoking Index (HSI), the Nicotine Dependence Syndrome Scale (NDSS), and the Hooked On Nicotine Checklist (HONC) were assessed, while plasma cotinine was measured as a biomarker of nicotine exposure in daily smokers. Univariate and multivariate associations were assessed by linear regression and multinomial logistic regression. Results In multivariate models, lower education was associated with higher FTND and HSI, income with HSI, and occupation with HSI (men only), FTND, HONC and NDSS scores. Lower education was related to higher cotinine levels among daily smokers, although the association diminished slightly after adjusting for daily smoking amount. Living without a spouse was associated with daily smoking and higher ND. Conclusion In this cross-sectional study low SES was linked with higher ND among current smokers, while low SES was associated with higher cotinine levels among daily smokers. Living alone was linked with higher ND. Longitudinal studies are warranted to further explore these associations. As lower SES smokers are more addicted they may need more targeted cessation services to succeed in quitting smoking.

Diurnal type (chronotype) differentiates individuals on an axis between the extremes of evening type to morning type. These diurnal-type preferences are thought to be relatively stable, but follow-up studies are sparse. The study aims were (1) to compare cross-sectional studies of diurnal type preferences between two decades and (2) to analyze the consistency of diurnal-type preferences using a longitudinal dataset. We analyzed a total of 18 087 adult males from four datasets with information on diurnal type and age. Of these, 2144 were available for survival analysis and 567 for analysis of longitudinal diurnal consistency. Diurnal type was assessed by asking the individual to what extent they would rate themselves a morning or an evening person, categorized into four groups. Statistical tests for stability of diurnal type were based on transition matrices and p values obtained using likelihood ratios. Cox regression was used to calculate the relative risk of all-cause mortality in each of the four diurn...

Few studies have examined predictors of nicotine replacement therapy (NRT) product use among adolescents. Using a population-based sample of 14- to 18-year-olds, we examined if self-rated addiction and Heaviness of Smoking Index (HSI) were associated with NRT use in 913 daily smokers. The ever-use prevalence of NRT was 24%. Boys smoked more cigarettes per day than girls and scored higher on HSI, but they perceived themselves to be less addicted. Compared to nonusers, a greater proportion of NRT users perceived themselves as addicted and demonstrated greater dependence on HSI. Perceiving oneself as addicted and having high HSI scores were associated with NRT use.

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 (Po1 � 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 (Po1 � 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.

Neuronal nicotinic acetylcholine receptor (nAChR) genes (CHRNA5/CHRNA3/CHRNB4) have been reproducibly associated with nicotine dependence, smoking behaviors, and lung cancer risk. Of the few reports that have focused on early smoking behaviors, association results have been mixed. This meta-analysis examines early smoking phenotypes and SNPs in the gene cluster to determine: (1) whether the most robust association signal in this region (rs16969968) for other smoking behaviors is also associated with early behaviors, and/or (2) if additional statistically independent signals are important in early smoking. We focused on two phenotypes: age of tobacco initiation (AOI) and age of first regular tobacco use (AOS). This study included 56,034 subjects (41 groups) spanning nine countries and evaluated five SNPs including rs1948, rs16969968, rs578776, rs588765, and rs684513. Each dataset was analyzed using a centrally generated script. Meta-analyses were conducted from summary statistics. AOS yielded significant associations with SNPs rs578776 (beta = 0.02, P = 0.004), rs1948 (beta = 0.023, P = 0.018), and rs684513 (beta = 0.032, P = 0.017), indicating protective effects. There were no significant associations for the AOI phenotype. Importantly, rs16969968, the most replicated signal in this region for nicotine dependence, cigarettes per day, and cotinine levels, was not associated with AOI (P = 0.59) or AOS (P = 0.92). These results provide important insight into the complexity of smoking behavior phenotypes, and suggest that association signals in the CHRNA5/A3/B4 gene cluster affecting early smoking behaviors may be different from those affecting the mature nicotine dependence phenotype. © 2013 WILEY PERIODICALS, INC.

Subjects with higher preference for evening hours in daily activities (eveningness) have been repeatedly shown to practice adverse health behaviors as compared to those preferring morning hours (morningness). However, associations between chronotype and dietary intake have not been explored intensively. The authors explored whether the human chronotype is associated with food and nutrient intakes in a random sample of the population aged 25 to 74 yrs. The cross-sectional study included 4493 subjects from the National FINRISK 2007 Study. Chronotype was assessed using a shortened version of Horne and Östberg's Morningness-Eveningness Questionnaire. Diet was assessed using a validated food frequency questionnaire. Associations between morningness-eveningness (ME) score and dietary intakes were analyzed by linear regression and difference between lowest (eveningness) and highest (morningness) ME score quintiles by Tukey's test. In the multivariable model, intakes of whole grain, rye, potatoes, and vegetables and roots decreased, whereas those of wine and chocolate increased with lower ME scores. Participants in the lowest ME score quintile consumed less fish (p .001) and fruits (p = .025) and more chocolate (p = .001) and soft drinks (p = .015) compared to the highest quintile. No linear association was found between ME score and total energy intake. In regression analyses, intake of alcohol (as a percentage of total energy intake; E%) and sucrose (E%) increased, whereas intake of carbohydrates (E%), protein (E%), fiber, folic acid, and sodium decreased with lower ME scores. Furthermore, participants in the lowest ME score quintile ingested more fat (E%) (p .001) and less vitamin D (p .001) compared to the highest quintile, even though no linear trend between ME score and these nutrients emerged. In conclusion, these results support existing evidence that individuals with circadian preference toward eveningness have less healthy lifestyles, such as unfavorable dietary habits, than those with tendency toward morningness, which could put them at higher risk of several chronic diseases.

Aims Smoking initiation during childhood or adolescence is strongly associated with friends’ smoking. Likewise, adverse living conditions increase the likelihood of future deviant behaviour. We examine whether smoking by a best friend and family members during school years as well as adverse childhood experiences are associated with smoking in adulthood. Data and Design We have analysed the responses of Finnish working-aged respondents in 1998 (N=25901) and 2003 (N=20773) to questions on the smoking status of friends and family members during school years as well as their answers on a six-item scale of childhood adversities. A case-control study design was used to compare current cigarette smokers (1998 and 2003) to non-smokers (1998 and 2003). Results If a best friend during school years was a smoker, the subject s odds ratio (OR) of being a smoker in adulthood was 4.43 among females and 3.91 among males compared to those with a non-smoking best friend in multivariate models adjusted for smoking by family members during school years and by six childhood adversities. These associations did not differ by age. Smoking in adulthood was associated with childhood adversities, most strongly with parental divorce or separation during the subjects’ school years. Conclusion Smoking by a best friend and parental divorce or separation during school years appears to be a strong factor of smoking in later life.

Most studies on lung function heritability have been conducted in smokers and non-smokers using cross-sectional study design. Smoking patterns may, however, confound the contribution of genetic factors. We investigated heritability of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio longitudinally, excluding the effects of smoking. A sample of never smoking female twins (n = 374), aged 63–76 at baseline, answered health questionnaires and attended spirometry in years 2000 and 2003. Bivariate structural equation modeling, restricted to adequate spirometry performances (baseline n = 339, follow-up n = 252), was used to estimate genetic and environmental influences on consecutive measurements of FEV1, FVC, and FEV1/FVC. The best-fitting models included additive genetic and non-shared environmental effects. Heritability estimates of 32% and 36% for FEV1, 41% and 37% for FVC, while 46% and 16% for FEV1/FVC were found at baseline and at follow-up. Genetic correlation between FEV1 and FEV1/FVC heritability estimates approached unity, whereas correlation between FVC estimates was 0.80. Environmental correlations were 0.69 for FEV1, 0.62 for FVC, and 0.07 for FEV1/FVC. In never smokers, additive genetic and non-shared environmental effects explain the inter-individual variations in FEV1, FVC, and FEV1/FVC. One third of the variation in FEV1 and FVC is explained by genetic and two thirds by environmental effects. Between 2000 and 2003, environmental effects on FEV1/FVC changed, and the proportion of variance explained by environmental effects increased remarkably. Genetic effects on FEV1 and FEV1/FVC are common to consecutive measurements, whereas at follow-up, new genetic factors explained 14% of the observed variance in FVC.

Studies by Breen et al. and Pergadia et al. find evidence for genetic linkage between major depressive disorder and the same region on chromosome 3. The linked region contains the gene GRM7, which encodes a protein for the metabotropic glutamate receptor 7 (mGluR7). Both studies used affected sibling pairs, and neither was able to replicate its finding using association studies in individuals from larger population-based studies. Other family-based studies have also failed to find a signal in this region. Furthermore, there are some differences in how the phenotype was classified, with Breen et al. finding evidence only in the most severely affected patients. Nonetheless, the finding is not without other substantive support. A meta-analysis of 3,957 case subjects with major depressive disorder and 3,428 control subjects from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D), Genetics of Recurrent Early-onset Depression (GenRED), and the Genetic Association Information Network-MDD (GAIN-MDD) data sets demonstrated a region of association for major depressive disorder within GRM7. Thus, the significance of this finding remains uncertain, although it points to a gene that might hold significant promise for further developments in studying the pathophysiology and treatment of major depressive disorder.

INTRODUCTION To obtain reliable information on nicotine and drug use through a population-based study, the prevalence of nicotine use in deceased young adults was studied in the Finnish postmortem toxicology database for a 3-year period. The nicotine user and non-nicotine user groups were compared by alcohol, drug, and drug-of-abuse findings and by the manner of death. METHODS Nicotine users were identified based on detection of nicotine, cotinine, and/or trans-3'-hydroxycotinine in urine from a population-based sample of deceased young adults aged 15-34 years at the time of death (n = 1,623, ∼60% of all fatalities). Background information from case referrals was used to distinguish the abuse of medicines from their therapeutic use. The manner of death was taken from death certificates. RESULTS Nicotine use was more common in young adults (75%) than among all cases in the database (55%). There were twice as many ethanol-positive cases in nicotine users (60%) than in non-nicotine users (30%). Nicotine use was common (70%-79%) among individuals on antipsychotics, antidepressants, anxiolytics, and/or hypnotics and sedatives. The proportion of nicotine users was also high among the drugs-of-abuse positive cases (85%). There were fewer deaths that were classified as natural in the nicotine users group. CONCLUSIONS Among deceased young adults, nicotine use was two to three times as common as has been estimated for the corresponding living population (20%-30%). Nicotine use was also strongly associated with substance abuse and mental illnesses requiring pharmacotherapy. This group of young adults usually cannot be reached by traditional health surveys.

Introduction: Genetic effects contribute to individual differ- ences in smoking behavior. Persistence to smoke despite known harmful health effects is mostly driven by nicotine addiction. As the physiological effects of nicotine are mediated by nicotinic acetylcholine receptors (nAChRs), we aimed at examining whether single nucleotide polymorphisms (SNPs) residing in nAChR subunit (CHRN) genes, other than CHRNA3/CHRNA5/ CHRNB4 gene cluster previously showing association in our sample, are associated with smoking quantity or serum cotinine levels. Methods: The study sample consisted of 485 Finnish adult daily smokers (age 30-75 years, 59% men) assessed for the number of cigarettes smoked per day (CPD) and serum cotinine level. We first studied SNPs residing on selected nAChR subunit genes (CHRNA2, CHRNA4, CHRNA6/CHRNB3, CHRNA7, CHRNA9, CHRNA10, CHRNB2, CHRNG/CHRND) genotyped within a genome-wide association study for single SNP and multiple SNP associations by ordinal regression. Next, we ex- plored individual haplotype associations using sliding window technique. Results: At one of the 8 loci studied, CHRNG/CHRND (chr2), single SNP (rs1190452), multiple SNP, and 2-SNP haplotype analyses (SNPs rs4973539-rs1190452) all showed statistically significant association with cotinine level. The median cotinine levels varied between the 2-SNP haplotypes from 220 ng/ml (AA haplotype) to 249 ng/ml (AG haplotype). We did not observe significant associations with CPD. Conclusions: These results provide further evidence that the g−d nAChR subunit gene region is associated with cotinine lev- els but not with the number of CPD, illustrating the usefulness of biomarkers in genetic analyses.

INTRODUCTION The association of smoking and depression is established, but it remains unclear which depression dimensions are linked to smoking patterns. METHODS The associations between smoking and depression dimensions were investigated among 4,980 male and 5,997 female Finnish twins. Longitudinal cigarette smoking patterns in 1975-1981 included multiple categories describing consistency and change. Depression was measured with the Beck Depression Inventory (BDI) in 1990. Preexisting depressed mood was screened with the life satisfaction scale strongly correlated with BDI. The BDI dimensions were negative attitudes toward self (NATS), performance impairment (PI), and weight loss (WL). Multiple logistic regressions and conditional logistic regressions for discordant twin pairs were conducted. RESULTS Controlling for confounders, two smoking patterns predicted all later depression dimensions. The NATS dimension showed a significant Sex × Smoking interaction: the associations of persistent smoking (odds ratio = 1.6, 95% CI = 1.3-2.0; p < .001) and inconsistent former (current in 1975 and former in 1981) smoking (1.6, 1.2-2.2; p = .001) with NATS remained significant among men only. Independently of gender, inconsistent former smoking predicted PI (1.2, 1.0-1.5; p = .04) and persistent smoking predicted WL (1.5, 1.3-1.8; p < .001). Consistent former smokers (former smokers in 1975 and 1981) had no elevated risk for any dimensions. Controlling for familial confounding, the association of persistent smoking with later NATS was replicated among discordant twin pairs (1.6, 1.1-2.2; p = .006). CONCLUSIONS Persistent smoking and inconsistent former smoking predict all depression dimensions, although such associations with the NATS dimension are independent among men only. Long-term abstinence (consistent former smoking) does not predict risk for any depression dimensions.

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 Fagerstrom 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.

The effects of smoking on periodontal biomarkers in adolescents are unknown. This study investigates matrix metalloproteinase (MMP)-8 and polymorphonuclear leukocyte elastase levels in saliva together with periodontal health indices accounting for body mass index and smoking in a birth cohort from Finland.The oral health of boys (n = 258) and girls (n = 243) aged 15 to 16 years was examined clinically. Health habits were assessed by questionnaire. Saliva samples were collected and analyzed by immunofluorometric and peptide assays for MMP-8 levels and polymorphonuclear leukocyte elastase activities, and investigated statistically with the background factors.Median MMP-8 values of male smokers were 112.03 microg/l compared to 176.89 microg/l of non-smokers (P = 0.05). For female smokers corresponding values were 170.88 microg/l versus 177.92 microg/l in non-smokers (not statistically significant). Elastase values in male smokers were 5.88 x 10(-3) Delta OD(405)/h versus 11.0 x 10(-3) Delta OD(405)/h in non-smokers (P = 0.02), and in female smokers 9.16 x 10(-3) Delta OD(405)/h versus 10.88 x 10(-3) Delta OD(405)/h in non-smokers (P = 0.72). The effect was strengthened by high pack-years of smoking (MMP-8, P = 0.04; elastase, P = 0.01). Both biomarkers increased with gingival bleeding. However, statistically significant associations were observed with bleeding on probing and MMP-8 (P = 0.04); MMP-8 was suggestively associated with probing depth (P = 0.09) in non-smoking boys. In smokers with calculus, MMP-8 increased after adjusting with body mass index (P = 0.03). No corresponding differences were seen in girls.Smoking significantly decreased both biomarkers studied. Compared to girls, boys seem to have enhanced susceptibility for periodontitis as reflected in salivary MMP-8 values.

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.

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.

Introduction The main body of smoking behavior research has targeted primarily moderate and heavy smoking. This study aimed to define characteristics of daily light smoking and to examine the consistency of this smoking pattern. Methods We examined light smoking among the Finnish adult population using longitudinal data from the Older Finnish Twin Cohort, collected in 1975, 1981, and 1990. We defined light smoking as fewer than 5 cigarettes/day and heavy smoking as 20 or more cigarettes per day. We examined the characteristics of light smokers in comparison to heavy smokers, studied which baseline features predicted change in the light smoking pattern, and described how this pattern changed over time. Results Among 9,940 current smokers in 1975, we identified 772 (7.8%) light smokers and 2,668 (26.9%) heavy smokers. Cross-sectionally, light smoking was characterized by female sex; younger age; higher education; lower consumption of alcohol, coffee, and other tobacco products; being single and physically active; and older age at smoking onset. Light smokers reported strong inhalation of cigarette smoke less often than did other smokers. Longitudinally, higher education, binge drinking, and moving in with a partner predicted changes in light smoking. The majority of the baseline light smokers were former, moderate, or heavy smokers at follow-ups, whereas only about 6% reported consistent light smoking throughout the 15-year study period. Discussion In long-term follow-up, consistent light smokers represent a relatively small fraction of smokers. This dynamic pattern of light smoking complicates inferences from studies of health consequences, suggesting that light smoking should not be evaluated based on a single assessment.

Aims: To examine whether smoking habits, nicotine dependence (ND) and plasma cotinine levels differ by diurnal type. Design: Data originated from the national FINRISK 2007 survey. Regression analyses were calculated to examine the association between diurnal type and smoking status, ND, and nicotine intake. Participants: 7091 FINRISK participants with smoking and diurnal type information and a subset of 1746 ever smokers with detailed smoking, and ND assessments. Measurements: Diurnal type assessed with a six-item sum scale was categorized as morning, intermediate and evening type. Smoking status was determined as current (daily or occasional), former, and never smokers. ND was measured with the Fagerstrom Test for Nicotine Dependence (FTND), the Hooked on Nicotine Checklist (HONC), and the Nicotine Dependence Syndrome Scale (NDSS). For current smokers, plasma cotinine was analyzed as biochemical measurement of nicotine intake. Findings: Evening type was associated with current smoking (OR=1.66, 95% CI 1.40, 1.97). A significant association with diurnal type was seen for FTND among men (beta= -0.46, 95% CI -0.72, -0.21), sexes combined for HONC (beta= -0.31, 95% CI -0.52, -0.11) and NDSS (beta= -0.86, 95% CI -1.43, -0.29) and for cotinine among men (beta= -0.73, 95% CI -1.16, -0.29). Adjustment for depressive symptoms attenuated the association of diurnal type with NDSS to be non-significant. Conclusions: Diurnal type was associated with multiple ND measures and nicotine intake, interestingly more so among men. Evening type persons are at higher risk of dependence, but depressive symptoms attenuates this association clearly.

The role of the nicotinic acetylcholine receptor gene cluster on chromosome 15q24-25 in the etiology of nicotine dependence (ND) is still being defined. In this study, we included all 15 tagging single nucleotide polymorphisms (SNPs) within the CHRNA5-CHRNA3-CHRNB4 cluster and tested associations with 30 smoking-related phenotypes.The study sample was ascertained from the Finnish Twin Cohort study. Twin pairs born 1938-1957 and concordant for a history of cigarette smoking were recruited along with their family members (mainly siblings), as part of the Nicotine Addiction Genetics consortium. The study sample consisted of 1,428 individuals (59% males) from 735 families, with mean age 55.6 years.We detected multiple novel associations for ND. DSM-IV ND symptoms associated significantly with the proxy SNP Locus 1 (rs2036527, p = .000009) and Locus 2 (rs578776, p = .0001) and tolerance factor of the Nicotine Dependence Syndrome Scale (NDSS) showed suggestive association to rs11636753 (p = .0059), rs11634351 (p = .0069), and rs1948 (p = .0071) in CHRNB4. Furthermore, we report significant association with DSM-IV ND diagnosis (rs2036527, p = .0003) for the first time in a Caucasian population. Several SNPs indicated suggestive association for traits related to ages at smoking initiation. Also, rs11636753 in CHRNB4 showed suggestive association with regular drinking (p = .0029) and the comorbidity of depression and ND (p = .0034).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.

INTRODUCTION Chromosome 20 has previously been associated with nicotine dependence (ND) and smoking cessation. Our aim was to replicate and extend these findings. METHODS First, a total of 759 subjects belonging to 206 Finnish families were genotyped with 18 microsatellite markers residing on chromosome 20, in order to replicate previous linkage findings. Then, the replication data were combined to an existing whole-genome linkage data resulting in a total of 1,302 genotyped subjects from 357 families. ND diagnosed by DSM-IV criteria, the Fagerstrom Test for Nicotine Dependence (FTND) score, and the lifetime maximum number of cigarettes smoked within a 24-hr period (MaxCigs24) were used as phenotypes in the nonparametric linkage analyses. RESULTS We replicated previously reported linkage to DSM-IV ND, with a maximum logarithm of odd (LOD) score of 3.8 on 20p11, with females contributing more (maximum LOD [MLOD] score 3.4 on 20q11) than males (MLOD score 2.6 on 20p11). With the combined sample, a suggestive LOD score of 2.3 was observed for DSM-IV ND on 20p11. Sex-specific analyses revealed that the signal was driven by females with a maximum LOD score of 3.3 (on 20q11) versus LOD score of 1.3 in males (on 20q13) in the combined sample. No significant linkage signals were obtained for FTND or MaxCigs24. CONCLUSIONS Our results provide further evidence that chromosome 20 harbors genetic variants influencing ND in adult smokers.

Evaluation and treatment of tobacco addiction among adolescents require partly different means than those for adults. Some adolescents are hooked already from the first cigarettes. Indicators of dependence designed for adults and based on regular smoking are suitable for daily smoking adolescents. Indicators providing a more sensitive detection of the appearance of the first signs of dependence are suitable for the less smoking. Regular meetings enabling an open discussion within personal or group councelling constitute the main components in the treatment of tobacco addiction in adolescents. Preliminary evidence exists also on the efficacy of supplementary nicotine patches and bupropion.

Food neophobia has been studied extensively in children, but its causal origins and relationship to eating behavior in adults are not well understood. We studied genetic and environmental effects on variation in food neophobia, measured using the Food Neophobia Scale, and explored associations between food neophobia and personality, pleasantness and use frequency of food groups, and body mass index in young adult twins (N = 1175, aged 20–25 years, 54.7% women). In women, additive genetic effects (heritability) accounted for 61% of variation in food neophobia, whereas in men, shared environmental effects explained 45% of the variation. Food neophobia negatively correlated with the personality trait Openness, corrected for the structural overlap (r = −0.23), and in women, these two traits had a genetic correlation (r g = −0.39). In addition, food neophobia negatively correlated with pleasantness and use frequency of fruits and vegetables and of fish and with mean pleasantness of foods. Once evolutionarily important, food neophobia should at present be considered in nutrition counseling as a possible barrier to a balanced diet.

We examined the effects of long-term smoking patterns on self-reported symptoms of chronic bronchitis within the Finnish adult twin cohort including 21, 609 individuals responding to questionnaires in 1975 and 1981, of which 11,015 respondents participated also in 1990. We also explored the association between smoking and bronchitis among discordant twin pairs. Among those without chronic bronchitis at baseline we examined incidence of chronic bronchitis in 1981 both by 1975 smoking status, but also based on subgroups formed according to change in smoking behaviors between 1975 and 1981. We conducted similar analyses in the longitudinal data including three consecutive measurements of smoking status. Logistic regressions demonstrated that among current smokers, the risk of chronic bronchitis increased about 1.5-fold by each amount category of daily cigarettes. When analyzing change of smoking status between 1975 and 1981, daily moderate and heavy smokers, smoking increasers and decreasers, as well as re-current smokers demonstrated elevated risks. In the analysis among discordant twin pairs the smoking co-twins had a 14-fold likelihood for chronic bronchitis compared to their never-smoking co-twins. Panel analyses showed that, not only moderate and heavy, but also former and light smokers, had significant risks for chronic bronchitis. Those with late smoking initiation, leisure time physical activity or over 10 years of smoking cessation were less likely to have chronic bronchitis. We conclude that in long term evaluation no safe level of smoking exists. Abstinence from tobacco seems to be the public health message justified by these results in prevention of chronic bronchitis.

Nicotine withdrawal (NW) is both an important contributor to difficulty quitting cigarettes and because of mood-related withdrawal symptoms a problem of particular relevance to psychiatry. Twin-studies suggest that genetic factors influence NW (heritability = 45%). Only one previous linkage study has published findings on NW [Swan et al. (2006); Am J Med Genet Part B 141B:354-360; LOD = 2.7; Chr. 6 at 159 cM]. As part of an international consortium, genome-wide scans (using over 360 autosomal microsatellite markers) and telephone diagnostic interviews were conducted on 289 Australian (AUS) and 161 Finnish (FIN, combined (COMB) N = 450 families) families ascertained from twin registries through index-cases with a lifetime history of cigarette smoking. The statistical approach used an affected-sib-pair design (at least two adult full siblings reported a history of DSM-IV NW) and conducted the linkage analyses using MERLIN. Linkage signals with LOD scores >1.5 were found on two chromosomes: 6 (FIN: LOD = 1.93 at 75 cM) and 11 at two different locations (FIN: LOD = 3.55 at 17 cM, and AUS: LOD = 1.68 with a COMB: LOD = 2.30 at 123 cM). The multipoint LOD score of 3.55 on chromosome 11p15 in FIN met genomewide significance (P = 0.013 with 1,000 simulations). At least four strong candidate genes lie within or near this peak on chromosome 11: DRD4, TPH, TH, and CHRNA10. Other studies have reported that chromosome 11 may harbor genes associated with various aspects of smoking behavior. This study adds to that literature by highlighting evidence for NW. © 2009 Wiley-Liss, Inc.

A cluster of three nicotinic acetylcholine receptor genes on chromosome 15 (CHRNA5/CHRNA3/CHRNB4) has been shown to be associated with nicotine dependence and smoking quantity. The aim of this study was to clarify whether the variation at this locus regulates nicotine intake among smokers by using the level of a metabolite of nicotine, cotinine, as an outcome. The number of cigarettes smoked per day (CPD) and immune-reactive serum cotinine level were determined in 516 daily smokers (age 30-75 years, 303 males) from the population-based Health2000 study. Association of 21 SNPs from a 100 kb region of chromosome 15 with cotinine and CPD was examined. SNP rs1051730 showed the strongest association to both measures. However, this SNP accounted for nearly a five-fold larger proportion of variance in cotinine levels than in CPD (R(2) 4.3% versus 0.9%). The effect size of the SNP was 0.30 for cotinine level, whereas it was 0.13 for CPD. Variation at CHRNA5/CHRNA3/CHRNB4 cluster influences nicotine level, measured as cotinine, more strongly than smoking quantity, measured by CPD, and appears thus to be involved in regulation of nicotine levels among smokers.

Smoking is a severe risk factor for periodontal health in adults, but data on the effect of smoking on periodontal health in teenage populations are sparse. The aim of this study was to investigate the effect of duration and quantity of smoking on periodontal health in teenagers and possible differences between genders.The oral health of 501 adolescents (15- to 16-year-old boys [n = 258] and girls [n = 243]) was examined. A structured questionnaire about self-reported smoking and health habits was filled out, and bitewing x-rays were taken. Clinical examinations included measuring periodontal indexes, such as visible plaque index, bleeding on probing, root calculus (RC), probing depth, and attachment loss. Results were analyzed by generalized linear logistic regression.Twenty-five percent of boys and 27% of girls were smokers. The boys and girls who smoked had higher RC values than non-smokers (P0.001). The adjusted scores for smoking boys and girls were 17.3 (95% confidence interval [CI]: 8.6 to 31.7) and 13.6 (95% CI: 5.5 to 29.7), respectively. The adjusted scores for non-smokers were 10.4 (95% CI: 5.7 to 18.3) and 7.7 (95% CI: 3.3 to 17.3), respectively. Smoking boys and girls also had more periodontal pocketsor =4 mm than non-smokers: the score for boys was 4.6 (95% CI: 2.2 to 9.1), and the score for girls was 5.4 (95% CI: 1.1 to 23.2; P0.001).Smoking significantly impaired periodontal health in teenagers.

Background: Changes in employment status may be associated with changes in health-related lifestyle, but population level research of such associations is very limited. This study aimed to determine associations between lifestyle and five employment trajectories, i.e. ‘stable’, ‘unstable’, ‘upward’ ‘downward’ and ‘chronic unemployment’. Methods: A cohort of 10 100 employees was followed up for 5 years. Associations of the employment trajectories with changes in smoking, alcohol drinking, body weight, physical activity and sleep duration were assessed with analysis of variance for repeated measures and pairwise post hoc comparisons. Results: Smoking was the only lifestyle component that was not associated with employment trajectory. In both genders, sleep duration decreased during chronic unemployment and among those on a downward employment trajectory. In men, alcohol consumption also increased in these two groups and body weight increased in the latter group. In women, physical activity decreased among those on a downward trajectory. In contrast, an upward labour market trajectory was associated with healthy or no changes in lifestyle both in men and women. Conclusion: Changes in lifestyle may contribute to development of the health gradients between the employed and unemployed, whereas unstable employment versus permanent employment does not incur risk of unhealthy lifestyle changes. In order to prevent widening of employment-related health inequalities, passages into employment should be facilitated and opportunities for health promotion should be improved among those trapped in or moving towards the labour market periphery.

The aim of the study was to examine whether smoking reduction over a 6-year period (1975-1981) predicted smoking cessation 9 years later by 1990. The longitudinal data from three surveys over 15-year period among the Finnish adult twin cohort were used. The data were collected by postal surveys in 1975, 1981, and 1990, and the sample comprised 11,015 participants, of whom 2,443 were persistent current smokers in 1975 and 1981. Smoking cessation by 1990 was examined as the outcome measure. Nineteen percent reported having stopped smoking by 1990, corresponding to an approximate annual rate of smoking cessation of 2%. Those who had quit smoking by 1990 had larger decreases in smoking between 1975 and 1981. The odds ratio for quitting by 1990 increased with increasing levels of reduction in amount smoked between 1975 and 1981. This was found in both categorical and trend analyses, and when adjusting for age, sex and for amount of baseline smoking. The model among twin pairs discordant for cessation indicated that the association of smoking reduction with increased likelihood of cessation was independent of genetic or early shared family influences on smoking behavior. We conclude that smokers who are able to decrease the number of cigarettes smoked per day by at least 25% are more likely to quit later.

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.

BACKGROUND Depression is associated with smoking, but the causality of the relationship is debated. The authors examine smoking behaviour as a predictor of depression among the Finnish adult twin population. METHOD Based on responses to surveys in 1975 and 1981, the authors characterized the subjects as never smokers, persistent former smokers, quitters, recurrent smokers and persistent smokers. The Beck Depression Inventory (BDI) was applied in 1990 to measure depression (BDI score >9). Although the population consisted of twins, the authors first considered the subjects as individuals. Logistic regression models were computed for 4164 men and 4934 women. In order to control for family and genetic background, conditional logistic regression analyses were conducted among twin pairs discordant for depression. Bivariate genetic modelling was used to examine genetic and environmental components of the correlation between smoking and depression. RESULTS Among the men, persistent smoking (OR 1 x 42, 95% CI 1 x 07-1 x 89) and smoking in 1975 but quitting by 1981 (OR 1 x 68, 95% CI 1 x 17-2 x 42) was associated with a higher risk of depression, while among the women only the quitters had an elevated risk (OR 1 x 38, 96% CI 1 x 01-1 x 87). The gender x smoking interaction showed persistent smoking to be a stronger risk for men. When family and genetic background were controlled, smoking remained a predictor of depression. Genetic modelling among the men suggested a modest correlation (rg=0 x 25) between genetic components of smoking and depression. CONCLUSIONS Smoking behaviour may be a gender-sensitive predictor of depression, the stronger association in men being partly accounted for by having underlying genes in common.

The Nicotine Dependence Syndrome Scale (NDSS) is a new multidimensional measure of nicotine dependence. The study aim was to examine the structure and heritability of the NDSS and its associations with nicotine dependence defined by FTND and DSM-IV criteria among Finnish smokers participating in an ongoing twin-family study. Adult twin pairs concordant for smoking from the Finnish Twin Cohort Study, and their siblings and parents were interviewed. Among 1370 smokers, the sum score of the NDSS (a summary measure of dependence) correlated moderately highly with FTND score (r = 0.62). Subjects in the highest NDSS sum score groups were more likely to be nicotine dependent according to DSM-IV criteria compared with those in the lowest quintile (odds ratio = 36.7, 95% confidence interval 13.0–103). In exploratory factor analysis, we derived three factors, named drive/priority, stereotypy/continuity and tolerance. The drive/priority factor correlated best with FTND (r = 0.54). Genetic modeling showed no differences in the genetic architecture of NDSS or FTND by gender; the overall heritability estimate for NDSS was 0.30 (95% CI 0.06–0.47), and for FTND 0.40 (95% CI 0.23–0.55). The sum score of the NDSS is moderately highly associated with DSM-IV nicotine dependence as well as FTND. These analyses indicate that the NDSS functions well in a Finnish family-based sample and provide additional validation of a new scale developed to capture complex behavioural features of nicotine dependence.

We studied socioeconomic status and marital status as predictors of smoking cessation, adjusting for previous smoking behavior and family background by using a large Finnish prospective twin dataset unselected for smoking behavior. The data were collected by postal surveys in 1981 and 1990, and the sample comprised 3,069 current smokers, of whom 20% had quit smoking by 1990. Logistic regression analyses of all twin individuals and conditional logistic regression analysis of discordant pairs were used to predict smoking cessation. High education predicted smoking cessation among both men (OR=2.32, 95% CI=1.31-4.10) and women (OR=3.98, 95% CI=1.85-8.51) as did high social class among women. Additionally, starting at a late age, smoking a small number of cigarettes per day, and a low level of nicotine per cigarette predicted cessation. Socioeconomic differences in cessation diminished only slightly when we adjusted for smoking behavior factors. Among the twin pairs who were discordant in terms of smoking cessation, the twin who continued smoking also smoked more on average at baseline (men: OR=.94, 95% CI=.89 -.99; women: OR=.82, 95% CI=.71-.94). The male twins who continued smoking had a smaller probability of getting married during the follow-up than had the cotwin who had quit smoking (OR=3.91, 95% CI=1.02-15.02). Indicators of socioeconomic status were important predictors of smoking cessation even when we adjusted for previous smoking behavior. For men, marriage was associated with an increased probability of cessation.

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.

Context Despite accumulating evidence that there is a genetic basis for cannabis use disorders (ie, abuse and dependence), few studies have identified genomic regions that may harbor biological risk and protective factors. Objective To conduct autosomal linkage analyses that identify genomic regions that may harbor genes conferring a vulnerability to cannabis use disorders. Design In 289 Australian families who participated in the Nicotine Addiction Genetics Project, 423 autosomal markers were genotyped. Families were ascertained for heavy cigarette smoking. Linkage was conducted for DSM-IV cannabis dependence and for a novel factor score representing problems with cannabis use, including occurrence of 3 of 4 abuse criteria (excluding legal problems) and 6 DSM-IV dependence criteria. Results A maximum logarithm of odds (LOD) of 3.36 was noted for the cannabis problems factor score on chromosome arm 1p. An LOD of 2.2 was noted on chromosome 4 in the region of the γ-aminobutyric acid type A gene cluster, including GABRA2, which has been implicated in drug use disorders. For DSM-IV cannabis dependence, a modest LOD score on chromosome 6 (1.42) near cannabinoid receptor 1 ( CNR1 ) was identified. In addition, support for an elevation on chromosome 3, identified in prior independent studies, was noted for the factor score and cannabis dependence (LOD, 1.4). Conclusions Genes such as ELTD1 on chromosome 1, in addition to genes on chromosomes 4 (eg, GABRA2) and 6 (eg, CNR1), may be associated with the genetic risk for cannabis use disorders. We introduce a novel quantitative phenotype, a cannabis problems factor score composed of DSM-IV abuse and dependence criteria, that may be useful for future linkage and association studies.

We conducted a genomewide linkage screen of a simple heavy-smoking quantitative trait, the maximum number of cigarettes smoked in a 24-h period, using two independent samples: 289 Australian and 155 Finnish nuclear multiplex families, all of which were of European ancestry and were targeted for DNA analysis by use of probands with a heavy-smoking phenotype. We analyzed the trait, using a regression of identity-by-descent allele sharing on the sum and difference of the trait values for relative pairs. Suggestive linkage was detected on chromosome 22 at 27-29 cM in each sample, with a LOD score of 5.98 at 26.96 cM in the combined sample. After additional markers were used to localize the signal, the LOD score was 5.21 at 25.46 cM. To assess the statistical significance of the LOD score in the combined sample, 1,000 simulated genomewide screens were conducted, resulting in an empirical P value of .006 for the LOD score of 5.21. This linkage signal is driven mainly by the microsatellite marker D22S315 (22.59 cM), which had a single-point LOD score of 5.41 in the combined sample and an empirical P value

The authors aimed to investigate factors associated with smoking cessation among adolescents after tobacco intervention. They examined smokers (n = 127) from one birth cohort (n = 545) in the city of Kotka in Finland. These smokers were randomized in 3 intervention groups the dentist (n = 44) and the school nurse (n = 42 groups), and a control group (n = 39). After 2 months, the authors sent a follow-up questionnaire to the initial smokers to find out who had quit.The authors found that those whose best friend was a nonsmoker were more likely to stop smoking (relative risk RR 7.0 95% Cl 4.6-10.7). Moreover, the nicotine-dependent participants (measured according to the Fagerström Test for Nicotine Dependence(36)) were less likely to stop (RR 0.1 95% Cl 0.08-0.11) compared to non-nicotine dependent participants. Last, of the diurnal types, the morning types found it easier to quit smoking than the evening types (RR 2.2 95% Cl 1.4-3.6). Thus, the authors concluded that the best friend''s influence, nicotine dependence, and diurnal type could be taken more into account in individual counseling on smoking cessation.

Background: The 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. Methods: The 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 casecontrol samples, were used for replication. Results: Rs2399496, 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 sixfold 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). Conclusions: Significant 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. © 2014 Korhonen et al.