Life-Course Associations Between Smoking and Depressive Symptoms. A 30-Year Finnish Follow-up Study.

INTRODUCTION: Relatively little is known about whether the association between smoking and depressive symptoms changes with age and how the trajectories of smoking and depressive symptoms are intertwined during the life course. In this population-based study, these associations were examined from young adulthood to middle age. METHODS: Participants of a Finnish cohort study (N = 1955) were assessed at the ages of 22, 32, 42, and 52 using questionnaires covering daily smoking (yes/no) and the short 13-item Beck Depression Inventory. Longitudinal latent class and longitudinal latent profile analyses were used to identify life course trajectories of smoking and depressive symptoms. RESULTS: The proportions of daily smokers decreased, while levels of depressive symptoms increased among both females and males from age 22 to 52 years. Smoking was associated with higher levels of depressive symptoms from age 22 to 42 years, while not at 52. Associations among males prevailed when adjusting for education, marital status, and alcohol use. Four life course classes of daily smoking (nonsmokers, decreasing prevalence of smoking, persistent smokers, and increasing prevalence of smoking) and four trajectories of depressive symptoms (low, increasing/moderate, decreasing/moderate, and high) were identified. In males, persistent daily smokers (relative risk ratio (RRR) = 4.5, 95% confidence interval (CI): 2.2 to 9.2) and those in the class with increasing smoking prevalence (RRR = 3.2, 95% CI: 1.1 to 9.1) had an increased risk of belonging to the high depressive symptoms profile. In females these associations were nonsignificant. CONCLUSIONS: Compared to females, the relationship between smoking and depressive symptoms seems more robust among males during adulthood. Specifically, males smoking persistently from young adulthood to middle age have an increased risk of high depressive symptoms trajectory. IMPLICATIONS: This population-based cohort with 30 years of follow-up showed that the life course trajectories of daily smoking and depressive symptoms are associated. Persistent daily smokers and those starting late had an increased risk of belonging to the profile with constantly high levels of depressive symptoms during the life course. However, these associations were statistically significant only in males. Actions should be strengthened, especially in males, to prevent smoking initiation, to help smoking cessation, and to identify and treat depression in smokers with significant depressive symptoms.

Self-reported sleep bruxism and mortality in 1990-2020 in a nationwide twin cohort.

BACKGROUND: The association of sleep bruxism with mortality has not been studied. OBJECTIVES: Altogether 12 040 subjects from the nationwide Finnish twin cohort were included in the analyses. We examined whether self-reported sleep bruxism is associated with increased risk of mortality, and if so, whether the effect is independent of known common risk factors. The time span of the follow-up was 30 years. METHODS: Cox proportional hazards regression models (Hazard Ratios and their 95% Confidence Intervals) adjusted by age, sex and covariates were used to assess the effect of baseline bruxism status in 1990 on future mortality in 1990-2020. RESULTS: The risk of mortality among all participants (n = 12 040), independent of missing covariates and adjusted by age and sex, was 40% higher in weekly bruxers than in never bruxers (HR 1.40, 95% CI 1.16-1.68, p < .001). However, when adjusted by all studied covariates, (n = 11 427) the risk was no longer observed (HR 1.04, 95% CI 0.86-1.25, p = .717). Despite the overall lack of between bruxism and mortality after adjustment for covariates, we examined the cause-specific risks for major cause-of-death groups. There were no substantial associations of weekly bruxism with major disease outcomes by the fully adjusted hazard ratios for them. CONCLUSION: Bruxism does not kill-in line with its definition of being rather a behaviour (with all its phenotypes) than a disease.

A Nationally Representative Study of the Hardening Hypothesis Among Educational Groups Over Four Decades.

INTRODUCTION: As smoking prevalence has decreased, there has been debate about "hardening" (smokers are more resistant to established tobacco control measures) or "softening" (smokers are more responsive to interventions) of the remaining smoking population. Despite growing evidence to reject the "hardening" hypothesis, there is lack of long-term population-based studies to test this hypothesis by educational level. AIMS AND METHODS: Repeated cross-sectional population-based surveys during 1978-2014 and in 2018 were utilized. The target population consisted of ~5000 25-64-year-old Finns annually. The data included 109 257 respondents of which 53 351 ever-smoking individuals were included in the analyses. Response rates varied between 84% and 43%. Five hardening indicators considering smoking frequency, intensity and smoking cessation were used as the dependent variables. The main independent variable was study year (time). Statistical analyses were based on regression models using restricted cubic splines by educational level. RESULTS: Contrary to the hardening hypothesis, hardening indicators showed softening over time among all educational groups. However, educational groups differed from each other. Compared with the highly educated, the quit ratio was lower, number of cigarettes per day (CPD) was higher, the proportions of daily smokers among current smokers and heavy smokers among daily smokers were higher among the less educated. CONCLUSIONS: In accordance with growing evidence, also the Finnish smoking population has "softened" over time. Although the change has been predominantly in the same direction for all educational groups, the rate of change has been stronger among the highly educated, highlighting the continued burden of smoking among the less educated. IMPLICATIONS: Even though "softening" of smoking has occurred, lighter smoking also poses health risks. Therefore, tobacco control policies and cessation services should be developed and targeted to a greater extent also for people who smoke less than daily and for those who smoke fewer CPD. Furthermore, interventions should focus on special requirements of the lower educational groups to promote health equity.

Changing genetic architecture of body mass index from infancy to early adulthood: an individual based pooled analysis of 25 twin cohorts.

BACKGROUND: Body mass index (BMI) shows strong continuity over childhood and adolescence and high childhood BMI is the strongest predictor of adult obesity. Genetic factors strongly contribute to this continuity, but it is still poorly known how their contribution changes over childhood and adolescence. Thus, we used the genetic twin design to estimate the genetic correlations of BMI from infancy to adulthood and compared them to the genetic correlations of height. METHODS: We pooled individual level data from 25 longitudinal twin cohorts including 38,530 complete twin pairs and having 283,766 longitudinal height and weight measures. The data were analyzed using Cholesky decomposition offering genetic and environmental correlations of BMI and height between all age combinations from 1 to 19 years of age. RESULTS: The genetic correlations of BMI and height were stronger than the trait correlations. For BMI, we found that genetic correlations decreased as the age between the assessments increased, a trend that was especially visible from early to middle childhood. In contrast, for height, the genetic correlations were strong between all ages. Age-to-age correlations between environmental factors shared by co-twins were found for BMI in early childhood but disappeared altogether by middle childhood. For height, shared environmental correlations persisted from infancy to adulthood. CONCLUSIONS: Our results suggest that the genes affecting BMI change over childhood and adolescence leading to decreasing age-to-age genetic correlations. This change is especially visible from early to middle childhood indicating that new genetic factors start to affect BMI in middle childhood. Identifying mediating pathways of these genetic factors can open possibilities for interventions, especially for those children with high genetic predisposition to adult obesity.

Exploring the relationships between adolescent alcohol misuse and later life health outcomes.

BACKGROUND: We sought to clarify the impact of adolescent alcohol misuse on adult physical health and subjective well-being. To do so, we investigated both the direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction and the indirect effects on these outcomes attributable to subsequent alcohol problems. METHOD: The sample included 2733 twin pairs (32% monozygotic; 52% female) from the FinnTwin16 study. Adolescent alcohol misuse was a composite of frequency of drunkenness, frequency of alcohol use, and alcohol problems at ages 16, 17, and 18.5. The early midlife outcomes included somatic symptoms, self-rated health, and life satisfaction at age 34. The mediators examined as part of the indirect effect analyses included alcohol problems from the Rutgers Alcohol Problem Index at ages 24 and 34. Serial mediation and co-twin comparison models were applied and included covariates from adolescence and early midlife. RESULTS: There were weak direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction. However, there was stronger evidence for indirect effects, whereby young adult and early midlife alcohol problems serially mediated the relationship between adolescent alcohol misuse and early midlife somatic symptoms (ß = 0.03, 95% CI [0.03, 0.04]), self-rated health (ß = -0.02, 95% CI [-0.03, -0.01]), and life satisfaction (ß = -0.03, CI [-0.04, -0.02]). These serial mediation effects were robust in co-twin comparison analyses. CONCLUSIONS: These results provide evidence that alcohol problems are a primary driver linking adolescent alcohol misuse and poor health outcomes across the lifespan.

Life course associations between smoking and depressive symptoms. A 30-year Finnish follow-up study.

BACKGROUND: While the association between smoking and depressive symptoms has been studied quite extensively, only little is known whether the association changes and how the trajectories of smoking and depressive symptoms are intertwined during the life course. In this population-based study, we examined these associations from young adulthood to middle age. METHODS: Participants of a Finnish cohort study (N = 1955) were addressed at ages 22, 32, 42 and 52 using postal questionnaires including questions of daily smoking and depressive symptoms (the short 13-item Beck Depression Inventory). Linear and logistic regression analyses and longitudinal latent class and profile analyses were used. RESULTS: The percentages of daily smokers decreased, while levels of depressive symptoms increased among both women and men from age 22 to 52 years. Daily smoking was associated with higher levels of depressive symptoms between ages 22 and 42, while not at age 52. Associations among men prevailed also in the adjusted models. Four life course trajectories of daily smoking (non-smokers, quitters, persistent smokers, and late starters) and four depressive symptoms (low, increasing/moderate, decreasing/moderate, and high) were identified. In the adjusted models, persistent daily smokers and late starters had significantly higher risk of belonging to the high depressive symptoms profile in men, but not in women. CONCLUSIONS: Compared to women the associations between daily smoking and depressive symptoms seem more robust among men during adulthood. Especially those men smoking persistently from young adulthood to middle age have an increased risk of high depressive symptoms trajectory during the life course.

Self-reported sleep bruxism in 1990 and 2011 in a nationwide twin cohort: Evidence of trait persistence and genetic liability.

BACKGROUND: Due to different assessment modes employed, a clear picture of the prevalence of sleep bruxism across time cannot be formed. Moreover, studies on the persistent or fluctuating nature of sleep bruxism have yielded divergent and even contradictory results. The aim of the present study was to evaluate in a nationwide twin cohort whether self-reported sleep bruxism was correlated longitudinally, pairwise and cross-twin over a 20-year period. OBJECTIVES: Self-reported bruxism was assessed in 1990 and 2011 by mailed questionnaires in the Finnish Twin Cohort study of same-sex twins born 1945-1957. METHODS: We assessed the phenotypic stability over time for all participating individuals (n = 4992). Among zygosity verified pairs (n = 516 MZ and n = 837 DZ), we estimated the cross-sectional zygosity correlations and the zygosity-specific cross-twin cross-time correlations. RESULTS: Reported bruxism appeared rather persistent over time without significant difference regarding zygosity. The overall phenotypic longitudinal correlation was 0.540 and somewhat higher in men (0.596) than in women (0.507). Pairwise trait correlations in 1990 and 2011 were higher in MZ than in DZ pairs. The cross-twin cross-time correlations were higher in MZ twins than in DZ twins, but less than the cross-sectional MZ and DZ pairwise correlations. CONCLUSIONS: The higher correlation of reported sleep bruxism in the cross-twin cross-time analyses in MZ than in DZ pairs implies a genetic background for bruxism persistence. Also, bruxism over time in individual twins appears to be fairly persistent and somewhat higher in men than women.

Factors contributing to psychological distress in the working population, with a special reference to gender difference.

BACKGROUND: Psychological distress refers to non-specific symptoms of stress, anxiety and depression, and it is more common in women. Our aim was to investigate factors contributing to psychological distress in the working population, with a special reference to gender differences. METHODS: We used questionnaire data from the nationally representative Finnish Regional Health and Well-being Study (ATH) collected in the years 2012-2016 (target population participants aged 20 +, n = 96,668, response rate 53%), restricting the current analysis to those persons who were working full-time and under 65 of age (n = 34,468). Psychological distress was assessed using the Mental Health Inventory-5 (MHI-5) (cut-off value <=52). We studied the following factors potentially associated with psychological distress: sociodemographic factors, living alone, having children under18 years of age, lifestyle-related factors, social support, helping others outside of the home and work-related factors. We used logistic regression analysis to examine association between having work-family conflict with the likelihood for psychological distress. We first performed the models separately for men and women. Then interaction by gender was tested in the combined data for those independent variables where gender differences appeared probable in the analyses conducted separately for men and women. RESULTS: Women reported more psychological distress than men (11.0% vs. 8.8%, respectively, p < 0.0001). Loneliness, job dissatisfaction and family-work conflict were associated with the largest risk of psychological distress. Having children, active participation, being able to successfully combine work and family roles, and social support were found to be protective factors. A significant interaction with gender was found in only two variables: ignoring family due to being absorbed in one's work was associated with distress in women (OR 1.30 (95% CI 1.00-1.70), and mental strain of work in men (OR 2.71 (95% CI 1.66-4.41). CONCLUSIONS: Satisfying work, family life and being able to successfully combine the two are important sources of psychological well-being for both genders in the working population.

Associations of sitting time with leisure-time physical inactivity, education, and body mass index change.

We aimed to investigate the associations of long-term leisure-time physical inactivity, body mass index (BMI) change, and education with sitting time in a 35-year follow-up based on self-reports in surveys. Influences of working status in 2011 and familial confounding on the associations were tested. Data were based on the population-based Finnish Twin Cohort of 5232 twins (53-67-year-old, 41% men) with four surveys in 1975-2011. Statistical analyses were performed using linear regression with several covariates. The effect of familial confounding (genetics and shared environment) was analyzed using a co-twin control design which should be interpreted as if familial confounding plays a role, an association should be seen among all individuals but not in discordant twin pairs. Compared to those not at work, those at work had a longer total sitting time/d. For those at work, higher education was associated with more total sitting but with less non-work sitting. Long-term leisure-time physical inactivity was associated with more non-work sitting among those at work, whereas long-term weight gain with more total and non-work sitting regardless of working status. Familial confounding attenuated the associations, except for the association of increasing BMI with total and non-work sitting among women at work. To conclude, total sitting time was longer among those still at work, but it was also influenced by long-term leisure-time physical inactivity, higher education, and an increase of BMI over the years. Public health efforts should be targeted to reduce sedentary behavior by promoting life-long leisure-time physical activity and weight control.

Correlates and genetics of self-reported sleep and awake bruxism in a nationwide twin cohort.

BACKGROUND: Sleep bruxism (SB) and awake bruxism (AB) have been considered different entities, although co-occurrence between them has been shown. While genetic factors have a marked influence on phenotypic variance in liability to SB, this remains unclear for AB. AIM: To examine the degree of co-occurrence of SB and AB, and whether they have common correlates and also twin similarity of SB and AB bruxism traits by zygosity and sex. METHODS: A questionnaire was mailed to all twins born 1945-1957 in Finland in 2012 (n = 11 766). Age and sex adjusted logistic regression models were used. Twin similarity was assessed using polychoric correlations, and crosstwin-crosstrait correlations were computed. RESULTS: The response rate was 72% (n = 8410). Any SB was reported by 14.8% and ≥ 3 nights weekly by 5.0%. Percentages for any AB were 18.4% and 6.3%, respectively. There was substantial co-occurrence (29.5%) between SB and AB, and several shared correlates were found. For SB, the polychoric intra-class correlation was 0.366 in monozygotic (MZ) and 0.200 in dizygotic (DZ) pairs, without gender difference. A twofold crosstwin-crosstrait correlation was observed in MZ twins compared to DZ twins. CONCLUSIONS: The risk factor profiles of SB and AB were largely but not entirely similar. The higher correlation in MZ than in DZ pairs suggests the influence of genetic factors on both SB and AB. The higher crosstwin-crosstrait correlation in MZ than in DZ pairs suggests some degree of genetic influences shared by SB and AB.

The Older Finnish Twin Cohort - 45 Years of Follow-up.

The older Finnish Twin Cohort (FTC) was established in 1974. The baseline survey was in 1975, with two follow-up health surveys in 1981 and 1990. The fourth wave of assessments was done in three parts, with a questionnaire study of twins born during 1945-1957 in 2011-2012, while older twins were interviewed and screened for dementia in two time periods, between 1999 and 2007 for twins born before 1938 and between 2013 and 2017 for twins born in 1938-1944. The content of these wave 4 assessments is described and some initial results are described. In addition, we have invited twin-pairs, based on response to the cohortwide surveys, to participate in detailed in-person studies; these are described briefly together with key results. We also review other projects based on the older FTC and provide information on the biobanking of biosamples and related phenotypes.

Association between education and future leisure-time physical inactivity: a study of Finnish twins over a 35-year follow-up.

BACKGROUND: Education is associated with health related lifestyle choices including leisure-time physical inactivity. However, the longitudinal associations between education and inactivity merit further studies. We investigated the association between education and leisure-time physical inactivity over a 35-year follow-up with four time points controlling for multiple covariates including familial confounding. METHODS: This study of the population-based Finnish Twin Cohort consisted of 5254 twin individuals born in 1945-1957 (59 % women), of which 1604 were complete same-sexed twin pairs. Data on leisure-time physical activity and multiple covariates was available from four surveys conducted in 1975, 1981, 1990 and 2011 (response rates 72 to 89 %). The association between years of education and leisure-time physical inactivity (<1.5 metabolic equivalent hours/day) was first analysed for each survey. Then, the role of education was investigated for 15-year and 35-year inactivity periods in the longitudinal analyses. The co-twin control design was used to analyse the potential familial confounding of the effects. All analyses were conducted with and without multiple covariates. Odds Ratios (OR) with 95 % Confidence Intervals (CI) were calculated using logistic and conditional (fixed-effects) regression models. RESULTS: Each additional year of education was associated with less inactivity (OR 0.94 to 0.95, 95 % CI 0.92, 0.99) in the cross-sectional age- and sex-adjusted analyses. The associations of education with inactivity in the 15- and 35-year follow-ups showed a similar trend: OR 0.97 (95 % CI 0.93, 1.00) and OR 0.94 (95 % CI 0.91, 0.98), respectively. In all co-twin control analyses, each year of higher education was associated with a reduced likelihood of inactivity suggesting direct effect (i.e. independent from familial confounding) of education on inactivity. However, the point estimates were lower than in the individual-level analyses. Adjustment for multiple covariates did not change these associations. CONCLUSIONS: Higher education is associated with lower odds of leisure-time physical inactivity during the three-decade follow-up. The association was found after adjusting for several confounders, including familial factors. Hence, the results point to the conclusion that education has an independent role in the development of long-term physical inactivity and tailored efforts to promote physical activity among lower educated people would be needed throughout adulthood.

Opioids, antiepileptic and anticholinergic drugs and the risk of fractures in patients 65 years of age and older: a prospective population-based study.

BACKGROUND: in men, the concomitant use of two or more benzodiazepines or two or more antipsychotics is associated with an increased risk of fracture(s). Potential associations between the concomitant use of drugs with central nervous system effects and fracture risk have not been studied. OBJECTIVE: the purpose was to describe the gender-specific risk of fractures in a population aged 65 years or over associated with the use of an opioid, antiepileptic or anticholinergic drug individually; or, their concomitant use with each other; or the concomitant use of one of these with a psychotropic drug. METHODS: this study was part of a prospective, population-based study performed in Lieto, Finland. Information about fractures in 1,177 subjects (482 men and 695 women) was confirmed with radiology reports. RESULTS: at 3 years of follow-up, the concomitant use of an opioid with an antipsychotic was associated with an increased risk of fractures in men. During the 6-year follow-up, the concomitant use of an opioid with a benzodiazepine was also related to the risk of fractures for males. No significant associations were found for females. CONCLUSION: the concomitant use of an opioid with an antipsychotic, or with a benzodiazepine may increase the risk of fractures in men aged 65 years and older.

Fractures as an independent predictor of functional decline in older people: a population-based study with an 8-year follow-up.

BACKGROUND: Fractures among older people are common, but there is scant evidence about the impact of fractures on functional decline in an unselected older population. OBJECTIVE: The objective of this study was to analyze the impact of lower and upper body fractures on functional performance among older adults during an 8-year follow-up. METHODS: A population-based cohort of 616 Finnish persons aged 65 and over was followed for up to 8 years, and the association between fractures and the risk of short-term (0-2 years) and long-term (up to 8 years) functional decline was analyzed. Fractures were categorized according their functional influence on mobility and activities of daily living (ADL) into lower and upper body fractures. Multivariate cumulative logistic regression model was used in the analyses. RESULTS: During the 8-year follow-up, 112 (18%) persons sustained at least one fracture. In the multivariate analyses, lower body fractures predicted both short-term and long-term decline in mobility [cumulative odds ratio (COR) 4.7, 95% confidence interval (95% CI) 1.9-11.7 and COR 2.6, 95% CI 1.1-6.2, respectively] and in ADL performance (COR 3.1, 95% CI 1.3-7.6 and COR 4.7, 95% CI 2.0-11.4, respectively). Upper body fractures predicted decline in ADL performance during the long-term follow-up (COR 2.5, 95% CI 1.3-4.8). Pre-fracture functional decline and inactivity in leisure time physical exercise were independently associated with the risk of decline in extensive activities. CONCLUSION: Fractures have an independent influence on the development of functional decline in older persons regardless of the pre-fracture health. Prevention of falls and fractures and improvement of treatment, rehabilitation and follow-up process after fractures are needed.

Smoking remains associated with education after controlling for social background and genetic factors in a study of 18 twin cohorts.

We tested the causality between education and smoking using the natural experiment of discordant twin pairs allowing to optimally control for background genetic and childhood social factors. Data from 18 cohorts including 10,527 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs discordant for education and smoking were analyzed by linear fixed effects regression models. Within twin pairs, education levels were lower among the currently smoking than among the never smoking co-twins and this education difference was larger within DZ than MZ pairs. Similarly, education levels were higher among former smoking than among currently smoking co-twins, and this difference was larger within DZ pairs. Our results support the hypothesis of a causal effect of education on both current smoking status and smoking cessation. However, the even greater intra-pair differences within DZ pairs, who share only 50% of their segregating genes, provide evidence that shared genetic factors also contribute to these associations.

The associations of smoking dependence motives with depression among daily smokers.

AIMS: To investigate how strongly smoking dependence and smoking dependence motives are associated with depressive symptoms among daily smokers and if these associations are independent of measured confounders and shared familial factors. DESIGN: Cross-sectional individual-based and within-pair analyses. SETTING: Fourth wave of the population-based Finnish Twin Cohort conducted in 2011. PARTICIPANTS: 918 daily smokers born 1945-1957 (48% men), mean age 59.5 years including 38 twin pairs discordant for depression. MEASUREMENTS: Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression scale with a cut off value ≥20 for depression. Smoking dependence was assessed using the Fagerström Test for Cigarette Dependence (FTCD) and smoking dependence motives with three subscales from the multi-dimensional Brief Wisconsin Inventory of Smoking Dependence Motives (WISDM): primary dependence motives (PDM), affective enhancement (AE), and Taste. Logistic regressions, using standardized scores of independent variables and adjusted for multiple confounders with correction for sampling as twin pairs, were used in the individual-based analyses. Conditional logistic regression was used to control for shared familial factors in discordant twin pairs. FINDINGS: Prevalence of depression was 18% (n = 163: 61 [14%] in men, n = 102 [22%] in women). Higher smoking dependence measured by the FTCD (OR 1.45; 95% CI 1.20, 1.75), and dependence motives measured by the PDM (1.56; 1.30, 1.87) and the AE (1.54; 1.28, 1.85) were associated with higher odds of depression. The associations remained after adjusting for individual confounders, except for neuroticism, which attenuated all associations. FTCD, PDM, and AE showed associations with depression within depression-discordant monozygotic pairs, suggesting an association independent of familial factors. CONCLUSIONS: Depression appears to be associated with smoking dependence and smoking dependence motives related to heavy, automatic use and use to regulate affective states. The associations appear to be confounded or mediated by neuroticism but are independent of shared familial influences.

Psychotropic drugs and the risk of fractures in old age: a prospective population-based study.

BACKGROUND: There is evidence that the use of any psychotropic and the concomitant use of two or more benzodiazepines are related to an increased risk of fractures in old age. However, also controversial results exist. The aim was to describe associations between the use of a psychotropic drug, or the concomitant use of two or more of these drugs and the risk of fractures in a population aged 65 years or over. METHODS: This study was a part of a prospective longitudinal population-based study carried out in the municipality of Lieto, South-Western Finland. The objective was to describe gender-specific associations between the use of one psychotropic drug [benzodiazepine (BZD), antipsychotic (AP) or antidepressant (AD)] or the concomitant use of two or more psychotropic drugs and the risk of fractures in a population 65 years or over. Subjects were participants in the first wave of the Lieto study in 1990-1991, and they were followed up until the end of 1996. Information about fractures confirmed with radiology reports in 1,177 subjects (482 men and 695 women) during the follow-up was collected from medical records. Two follow-up periods (three and six years) were used, and previously found risk factors of fractures were adjusted as confounding factors separately for men and women. The Poisson regression model was used in the analyses. RESULTS: The concomitant use of two or more BZDs and the concomitant use of two or more APs were related to an increased risk of fractures during both follow-up periods after adjusting for confounding factors in men. No similar associations were found in women. CONCLUSIONS: The concomitant use of several BZDs and that of several APs are associated with an increase in the risk of fractures in older men. Our findings show only risk relations. We cannot draw the conclusion that these drug combinations are causes of fractures.

Parental Education and Genetics of BMI from Infancy to Old Age: A Pooled Analysis of 29 Twin Cohorts.

OBJECTIVE: The objective of this study was to analyze how parental education modifies the genetic and environmental variances of BMI from infancy to old age in three geographic-cultural regions. METHODS: A pooled sample of 29 cohorts including 143,499 twin individuals with information on parental education and BMI from age 1 to 79 years (299,201 BMI measures) was analyzed by genetic twin modeling. RESULTS: Until 4 years of age, parental education was not consistently associated with BMI. Thereafter, higher parental education level was associated with lower BMI in males and females. Total and additive genetic variances of BMI were smaller in the offspring of highly educated parents than in those whose parents had low education levels. Especially in North American and Australian children, environmental factors shared by co-twins also contributed to the higher BMI variation in the low education level category. In Europe and East Asia, the associations of parental education with mean BMI and BMI variance were weaker than in North America and Australia. CONCLUSIONS: Lower parental education level is associated with higher mean BMI and larger genetic variance of BMI after early childhood, especially in the obesogenic macro-environment. The interplay among genetic predisposition, childhood social environment, and macro-social context is important for socioeconomic differences in BMI.

Association of current and former smoking with body mass index: A study of smoking discordant twin pairs from 21 twin cohorts.

BACKGROUND: Smokers tend to weigh less than never smokers, while successful quitting leads to an increase in body weight. Because smokers and non-smokers may differ in genetic and environmental family background, we analysed data from twin pairs in which the co-twins differed by their smoking behaviour to evaluate if the association between smoking and body mass index (BMI) remains after controlling for family background. METHODS AND FINDINGS: The international CODATwins database includes information on smoking and BMI measured between 1960 and 2012 from 156,593 twin individuals 18-69 years of age. Individual-based data (230,378 measurements) and data of smoking discordant twin pairs (altogether 30,014 pairwise measurements, 36% from monozygotic [MZ] pairs) were analysed with linear fixed-effects regression models by 10-year periods. In MZ pairs, the smoking co-twin had, on average, 0.57 kg/m2 lower BMI in men (95% confidence interval (CI): 0.49, 0.70) and 0.65 kg/m2 lower BMI in women (95% CI: 0.52, 0.79) than the never smoking co-twin. Former smokers had 0.70 kg/m2 higher BMI among men (95% CI: 0.63, 0.78) and 0.62 kg/m2 higher BMI among women (95% CI: 0.51, 0.73) than their currently smoking MZ co-twins. Little difference in BMI was observed when comparing former smoking co-twins with their never smoking MZ co-twins (0.13 kg/m2, 95% CI 0.04, 0.23 among men; -0.04 kg/m2, 95% CI -0.16, 0.09 among women). The associations were similar within dizygotic pairs and when analysing twins as individuals. The observed series of cross-sectional associations were independent of sex, age, and measurement decade. CONCLUSIONS: Smoking is associated with lower BMI and smoking cessation with higher BMI. However, the net effect of smoking and subsequent cessation on weight development appears to be minimal, i.e. never more than an average of 0.7 kg/m2.