Distinct loci in the CHRNA5/CHRNA3/CHRNB4 gene cluster are associated with onset of regular smoking.

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.

Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory.

Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.

Chromosome 20 shows linkage with DSM-IV nicotine dependence in Finnish adult smokers.

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 Fagerström 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.

Analysis of detailed phenotype profiles reveals CHRNA5-CHRNA3-CHRNB4 gene cluster association with several nicotine dependence traits.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Association of serum cotinine level with a cluster of three nicotinic acetylcholine receptor genes (CHRNA3/CHRNA5/CHRNB4) on chromosome 15.

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.

Food neophobia in young adults: genetic architecture and relation to personality, pleasantness and use frequency of foods, and body mass index--a twin study.

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.

Cigarette smoking and dimensions of depressive symptoms: longitudinal analysis among Finnish male and female twins.

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.

Nicotine, alcohol, and drug findings in young adults in a population-based postmortem database.

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.

Associations of nicotine intake measures with CHRN genes in Finnish smokers.

INTRODUCTION: Genetic effects contribute to individual differences 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 explored 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 γ-δ nAChR subunit gene region is associated with cotinine levels but not with the number of CPD, illustrating the usefulness of biomarkers in genetic analyses.

Heritability of lung function: a twin study among never-smoking elderly women.

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.

[Evaluation of tobacco addiction among adolescents and its treatment within the health care]. / Nuorten tupakkariippuvuuden arviointi ja hoito terveydenhuollossa.

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.

Characteristics and health consequences of intermittent smoking: long-term follow-up among Finnish adult twins.

INTRODUCTION: The definition of a smoker as someone who smokes daily has been challenged. No consensus exists regarding whether intermittent smoking represents transition toward daily smoking or cessation or whether intermittent smokers consistently maintain their low tobacco use frequency. Although abundant evidence supports the adverse health consequences of daily smoking, less evidence is available on intermittent smoking. METHODS: We examined characteristics and health consequences of intermittent cigarette smoking among Finnish adult twins. We used longitudinal data of 21,340 persons with smoking status from questionnaires in 1975 and 1981 and data on lung cancer incidence from 1982 to 2004 from the Finnish Cancer Registry. RESULTS: We identified 641 consistent intermittent smokers comprising 3% of the study population. Consistent intermittent smokers had higher education, less use of other tobacco products, healthier lifestyles, and partly more favorable mental health profiles compared with lifetime regular smokers. However, in terms of other lifestyle factors, intermittent smokers compared mostly unfavorably with never-smokers, despite being better educated. Intermittent smoking showed substantial heritability. There were 213 incident lung cancer cases among all study subjects; only one case was found among the intermittent smokers. The sex- and age-adjusted hazard ratios of lung cancer were not significantly elevated for the intermittent smokers, but they were increased more than 10-fold for all other smokers. DISCUSSION: Although the present study did not find evidence of elevated lung cancer risk among intermittent smokers, compared with never-smokers, further studies should investigate other health consequences of intermittent smoking, such as cardiovascular and nonmalignant pulmonary outcomes.

Characteristics and consistency of light smoking: long-term follow-up among Finnish adults.

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.

Long-term smoking behavior patterns predicting self-reported chronic bronchitis.

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.

Key factors in smoking cessation intervention among 15-16-year-olds.

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.

Genetic linkage findings for DSM-IV nicotine withdrawal in two populations.

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.

The effect of smoking on periodontal health of 15- to 16-year-old adolescents.

BACKGROUND: 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. METHODS: 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. RESULTS: Twenty-five percent of boys and 27% of girls were smokers. The boys and girls who smoked had higher RC values than non-smokers (P <0.001). 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 pockets > or =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; P <0.001). CONCLUSION: Smoking significantly impaired periodontal health in teenagers.

Employment trajectory as determinant of change in health-related lifestyle: the prospective HeSSup study.

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 Nicotine Dependence Syndrome Scale in Finnish smokers.

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.

Genetic architecture of smoking behavior: a study of Finnish adult twins.

Both genetic and environmental factors affect smoking initiation and maintenance, but less is known about the genetic architecture of various other smoking-related behaviors. The aim of this study is to examine the genetic architecture of smoking behavior in a large twin cohort. Questionnaires with an extensive smoking history section were mailed to same-sex adult twins of the Finnish twin cohort. The final study population included 2923 monozygotic and 6018 dizygotic twin pairs aged 24 to 88 years. Two-stage bivariate genetic modeling of age at initiation with amount smoked (less than 20 cigarettes per day vs. 20 or more) and age at initiation with smoking cessation was done by using the Mx statistical package. For men the heritability estimate for age at initiation was .59 (95% confidence interval [CI] .49-.69), for amount smoked .54 (95% CI .45-.62) and for smoking cessation .58 (95% CI .50-.65). For women the heritability estimates were .36 (95% CI .28-.43), .61 (95% CI .46-.70) and .50 (95% CI .39-.60), respectively. The genetic correlations between age at initiation and amount smoked or smoking cessation were at most .22 in magnitude, indicating that genetic influences in age at initiation accounted for at most about 4% of the genetic factors in amount smoked or in cessation. Genetic factors are important in amount smoked and smoking cessation and they are largely independent of genetic influences on age at initiation. This has implications for defining phenotypes in searches for genes underlying smoking behaviors.