General practitioners ending their practice and impact on patients' health, healthcare use and mortality: a protocol for national registry cohort studies in Norway, 2008 to 2021.

INTRODUCTION: Continuous general practitioner (GP) and patient relations associate with positive health outcomes. Termination of GP practice is unavoidable, while consequences of final breaks in relations are less explored. We will study how an ended GP relation affects patient's healthcare utilisation and mortality compared with patients with a continuous GP relation. METHODS AND ANALYSIS: We link national registries data on individual GP affiliation, sociodemographic characteristics, healthcare use and mortality. From 2008 to 2021, we identify patients whose GP stopped practicing and will compare acute and elective, primary and specialist healthcare use and mortality, with patients whose GP did not stop practicing. We match GP-patient pairs on age and sex (both), immigrant status and education (patients), and number of patients and practice period (GPs). We analyse the outcomes before and after an ended GP-patient relation, using Poisson regression with high-dimensional fixed effects. ETHICS AND DISSEMINATION: This study protocol is part of the approved project Improved Decisions with Causal Inference in Health Services Research, 2016/2159/REK Midt (the Regional Committees for Medical and Health Research Ethics) and does not require consent. HUNT Cloud provides secure data storage and computing. We will report using the STROBE guideline for observational case-control studies and publish in peer-reviewed journals, accessible in NTNU Open and present at scientific conferences. To reach a broader audience, we will summarise articles in the project's web page, regular and social media, and disseminate to relevant stakeholders.

Intergenerational polygenic obesity risk throughout adolescence in a cross-sectional study design: The HUNT study, Norway.

OBJECTIVE: This study examined the relationship between parental obesity polygenic risk and children's BMI throughout adolescence. Additionally, from a smaller subsample, the objective was to assess whether parental polygenic risk score (PRS) may act as a proxy for offspring PRS in studies lacking offspring genetic data. METHODS: A total of 8,561 parent-offspring (age 13-19 years) trios from the Trøndelag Health Study (the HUNT Study) were included, of which, 1,286 adolescents had available genetic data. Weighted parental PRSs from 900 single-nucleotide polymorphisms robustly associated with adult BMI were constructed and applied in linear mixed-effects models. RESULTS: A positive association between parental PRS and offspring sex- and age-adjusted BMI (iso-BMI) throughout adolescence was identified. The estimated marginal effects per standard deviation increase in parental PRS were 0.26 (95% CI: 0.18-0.33), 0.36 (95% CI: 0.29-0.43), and 0.62 kg/m2 (95% CI: 0.51-0.72) for maternal, paternal, and combined parental PRS, respectively. In subsample analyses, the magnitude of association of the parental PRS versus offspring PRS with iso-BMI in adolescents was similar. CONCLUSIONS: Parental PRS was consistently associated with offspring iso-BMI throughout adolescence. Results from subsample analyses support the use of parental PRS of obesity as a proxy for adolescent PRS in the absence of offspring genetic data.

Socioeconomic Position, Multimorbidity and Mortality in a Population Cohort: The HUNT Study.

Multimorbidity and socioeconomic position are independently associated with mortality. We investigated the association of occupational position and several multimorbidity measures with all-cause mortality. A cohort of people aged 35 to 75 years who participated in the Trøndelag Health Study in 2006-2008 and had occupational data was linked to the Norwegian National Population Registry for all-cause mortality from study entry until 1 February 2019. Logistic regression models for each occupational group were used to analyze associations between the number of conditions and 10-year risk of death. Cox regression models were used to examine associations between combinations of multimorbidity, occupational position, and mortality. Analyses were conducted for men and women. Included were 31,132 adults (16,950 women (54.4%)); occupational groups: high, 7501 (24.1%); low, 15,261 (49.0%)). Increased mortality was associated with lower occupational group, more chronic conditions, and all multimorbidity measures. The joint impact of occupational group and multimorbidity on mortality was greater in men than women. All multimorbidity measures are strongly associated with mortality, with varying occupational gradients. Social differences in multimorbidity are a public health challenge and necessitate consideration in health care. Men in lower occupational groups seem to be a particularly vulnerable group.

Socioeconomic inequalities in the prevalence of complex multimorbidity in a Norwegian population: findings from the cross-sectional HUNT Study.

OBJECTIVES: Multimorbidity, the co-occurrence of multiple long-term conditions, is common and increasing. Definitions and assessment methods vary, yielding differences in estimates of prevalence and multimorbidity severity. Sociodemographic characteristics are associated with complicating factors of multimorbidity. We aimed to investigate the prevalence of complex multimorbidity by sex and occupational groups throughout adulthood. DESIGN: Cross-sectional study. SETTING: The third total county survey of The Nord-Trøndelag Health Study (HUNT), 2006-2008, Norway. PARTICIPANTS: Individuals aged 25-100 years with classifiable occupational data and complete questionnaires and measurements. OUTCOME MEASURE: Complex multimorbidity defined as 'the co-occurrence of three or more chronic conditions affecting three or more different body (organ) systems within one person without defining an index chronic condition'. ANALYSIS: Logistic regression models with age and occupational group were specified for each sex separately. RESULTS: 38 027 of 41 193 adults (55% women) were included in our analyses. 54% of the participants were identified as having complex multimorbidity. Prevalence differences in percentage points (pp) of those in the low occupational group (vs the high occupational group (reference)) were 19 (95% CI, 16 to 21) pp in women and 10 (8 to 13) pp in men at 30 years; 12 (10 to 14) pp in women and 13 (11 to 15) pp in men at 55 years; and 2 (-1 to 4) pp in women and 7 (4 to 10) pp in men at 75 years. CONCLUSION: Complex multimorbidity is common from early adulthood, and social inequalities persist until 75 years in women and 90 years in men in the general population. These findings have policy implications for public health as well as healthcare, organisation, treatment, education and research, as complex multimorbidity breaks with the specialised, fragmented paradigm dominating medicine today.

Changes in General Practitioners' consultation frequency over time for patients with hypertension or anxiety/depression symptoms: a 10-year follow-up of the Norwegian HUNT study.

BACKGROUND: General Practitioners' (GPs') workload has been suggested to increase in many countries; how does this impact patient follow-up? OBJECTIVE: To investigate trends in GP consultation patterns for adults according to baseline hypertension and anxiety/depression symptoms and attribution of the GP to trend differences. METHODS: Prospective cohort study, linking survey data and clinical measurements from the Norwegian HUNT3 study (2006-08) with national administrative data on GP list assignment and consultations with GP services. We grouped participants aged 40-59 years according to sex and their baseline status regarding hypertension and anxiety/depression symptoms. We registered GP consultations in 2007-16 and used general estimation equation models to estimate the level of GP consultations per month per year during follow-up. We used multilevel models with participants nested in their assigned regular GP to calculate GP-level intra-class correlation coefficients, reflecting to what extent patients' consultation patterns could be attributed to the individual GP. RESULTS: In total, 47 550 HUNT3 participants were registered with 102 different GPs in Nord-Trøndelag County, Norway, in 2007. Adjusted for age, we observed an overall increase in GP consultations in 2007-16, particularly in those with a better health status at baseline. About 2% of the variance of patient consultations could be attributed to differences between GPs and 10% to the use of lengthy consultations. Out-of-hours consultations did not change much in the study period 2007-16. CONCLUSION: Increased use of GP consultations, mainly among the healthiest participants, encourage further research into whether these patients displace patients with heavier and more complex needs.

Contact with primary health care physicians before an acute hospitalisation.

Objectives: To assess contacts with general practitioners (GPs), both regular GPs and out-of-hours GP services (OOH) during the year before an emergency hospital admission. Design: Longitudinal design with register-based information on somatic health care contacts and use of municipality health care services. Setting: Four municipalities in central Norway, 2012-2013. Subjects: Inhabitants aged 50 and older admitted to hospital for acute myocardial infarction, hip fracture, stroke, heart failure, or pneumonia. Main outcome measures: GP contact during the year and month before an emergency hospital admission. Results: Among 66,952 identified participants, 720 were admitted to hospital for acute myocardial infarction, 645 for hip fracture, 740 for stroke, 399 for heart failure, and 853 for pneumonia in the two-year study period. The majority of these acutely admitted patients had contact with general practitioners each month before the emergency hospital admission, especially contacts with a regular GP. A general increase in GP contact was observed towards the time of hospital admission, but development differed between the patient groups. Patients admitted with heart failure had the steepest increase of monthly GP contact. A sizable percentage did not contact the regular GP or OOH services the last month before admission, in particular men aged 50-64 admitted with myocardial infarction or stroke. Conclusion: The majority of patients acutely admitted to hospital for different common severe emergency diagnoses have been in contact with GPs during the month and year before the admission. This points towards general practitioners having an important role in these patients' health care. KEY MESSAGES There is scarce knowledge about primary health care contact before an emergency hospital admission. The percentage of patients with contacts differed between patient groups, and increased towards hospital admission for most diagnoses, particularly heart failure. More than 50% having monthly general practitioner contact before admission underscores the general practitioners' role in these patients' health care. Our results underscore the need to consider medical diagnosis when talking about the role of general practitioners in preventing emergency hospital admissions.

Body mass index and all cause mortality in HUNT and UK Biobank studies: linear and non-linear mendelian randomisation analyses.

OBJECTIVE: To investigate the shape of the causal relation between body mass index (BMI) and mortality. DESIGN: Linear and non-linear mendelian randomisation analyses. SETTING: Nord-Trøndelag Health (HUNT) Study (Norway) and UK Biobank (United Kingdom). PARTICIPANTS: Middle to early late aged participants of European descent: 56 150 from the HUNT Study and 366 385 from UK Biobank. MAIN OUTCOME MEASURES: All cause and cause specific (cardiovascular, cancer, and non-cardiovascular non-cancer) mortality. RESULTS: 12 015 and 10 344 participants died during a median of 18.5 and 7.0 years of follow-up in the HUNT Study and UK Biobank, respectively. Linear mendelian randomisation analyses indicated an overall positive association between genetically predicted BMI and the risk of all cause mortality. An increase of 1 unit in genetically predicted BMI led to a 5% (95% confidence interval 1% to 8%) higher risk of mortality in overweight participants (BMI 25.0-29.9) and a 9% (4% to 14%) higher risk of mortality in obese participants (BMI ≥30.0) but a 34% (16% to 48%) lower risk in underweight (BMI <18.5) and a 14% (-1% to 27%) lower risk in low normal weight participants (BMI 18.5-19.9). Non-linear mendelian randomisation indicated a J shaped relation between genetically predicted BMI and the risk of all cause mortality, with the lowest risk at a BMI of around 22-25 for the overall sample. Subgroup analyses by smoking status, however, suggested an always-increasing relation of BMI with mortality in never smokers and a J shaped relation in ever smokers. CONCLUSIONS: The previously observed J shaped relation between BMI and risk of all cause mortality appears to have a causal basis, but subgroup analyses by smoking status revealed that the BMI-mortality relation is likely comprised of at least two distinct curves, rather than one J shaped relation. An increased risk of mortality for being underweight was only evident in ever smokers.

Maternal Smoking in Pregnancy and Offspring Depression: a cross cohort and negative control study.

Previous reports suggest that offspring of mothers who smoke during pregnancy have greater risk of developing depression. However, it is unclear whether this is due to intrauterine effects. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) from the UK (N = 2,869), the Nord-Trøndelag health study (HUNT) from Norway (N = 15,493), the Pelotas 1982 Birth Cohort Study from Brazil (N = 2,626), and the Swedish Sibling Health Cohort (N = 258 sibling pairs), we compared associations of maternal smoking during pregnancy and mother's partner's smoking during pregnancy with offspring depression and performed a discordant sibling analysis. In meta-analysis, maternal smoking during pregnancy was associated with higher odds of offspring depression (OR 1.20, 95% CI:1.08,1.34), but mother's partner's smoking during pregnancy was not (OR 1.05, 95% CI:0.94,1.17). However, there was only weak statistical evidence that the odds ratios for maternal and mother's partner's smoking differed from each other (p = 0.08). There was no clear evidence for an association between maternal smoking during pregnancy and offspring depression in the sibling analysis. Findings do not provide strong support for a causal role of maternal smoking during pregnancy in offspring depression, rather observed associations may reflect residual confounding relating to characteristics of parents who smoke.

Heavier smoking increases coffee consumption: findings from a Mendelian randomization analysis.

Background: There is evidence for a positive relationship between cigarette and coffee consumption in smokers. Cigarette smoke increases metabolism of caffeine, so this may represent a causal effect of smoking on caffeine intake. Methods: We performed Mendelian randomization analyses in the UK Biobank (N = 114 029), the Norwegian HUNT study (N = 56 664) and the Copenhagen General Population Study (CGPS) (N = 78 650). We used the rs16969968 genetic variant as a proxy for smoking heaviness in all studies and rs4410790 and rs2472297 as proxies for coffee consumption in UK Biobank and CGPS. Analyses were conducted using linear regression and meta-analysed across studies. Results: Each additional cigarette per day consumed by current smokers was associated with higher coffee consumption (0.10 cups per day, 95% CI: 0.03, 0.17). There was weak evidence for an increase in tea consumption per additional cigarette smoked per day (0.04 cups per day, 95% CI: -0.002, 0.07). There was strong evidence that each additional copy of the minor allele of rs16969968 (which increases daily cigarette consumption) in current smokers was associated with higher coffee consumption (0.16 cups per day, 95% CI: 0.11, 0.20), but only weak evidence for an association with tea consumption (0.04 cups per day, 95% CI: -0.01, 0.09). There was no clear evidence that rs16969968 was associated with coffee or tea consumption in never or former smokers or that the coffee-related variants were associated with cigarette consumption. Conclusions: Higher cigarette consumption causally increases coffee intake. This is consistent with faster metabolism of caffeine by smokers, but could also reflect a behavioural effect of smoking on coffee drinking.

Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium.

Observational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects. We examined the causal effect of smoking on hay fever and asthma by using the smoking-associated single nucleotide polymorphism (SNP) rs16969968/rs1051730. We included 231,020 participants from 22 population-based studies. Observational analyses showed that current vs never smokers had lower risk of hay fever (odds ratio (OR) = 0·68, 95% confidence interval (CI): 0·61, 0·76; P < 0·001) and allergic sensitization (OR = 0·74, 95% CI: 0·64, 0·86; P < 0·001), but similar asthma risk (OR = 1·00, 95% CI: 0·91, 1·09; P = 0·967). Mendelian randomization analyses in current smokers showed a slightly lower risk of hay fever (OR = 0·958, 95% CI: 0·920, 0·998; P = 0·041), a lower risk of allergic sensitization (OR = 0·92, 95% CI: 0·84, 1·02; P = 0·117), but higher risk of asthma (OR = 1·06, 95% CI: 1·01, 1·11; P = 0·020) per smoking-increasing allele. Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.

Premature Adult Death in Individuals Born Preterm: A Sibling Comparison in a Prospective Nationwide Follow-Up Study.

BACKGROUND: Close to one in ten individuals worldwide is born preterm, and it is important to understand patterns of long-term health and mortality in this group. This study assesses the relationship between gestational age at birth and early adult mortality both in a nationwide population and within sibships. The study adds to existing knowledge by addressing selected causes of death and by assessing the role of genetic and environmental factors shared by siblings. METHODS: Study population was all Norwegian men and women born from 1967 to 1997 followed using nation-wide registry linkage for mortality through 2011 when they were between 15 and 45 years of age. Analyses were performed within maternal sibships to reduce variation in unobserved genetic and environmental factors shared by siblings. Specific outcomes were all-cause mortality and mortality from cardiovascular diseases, cancer and external causes including accidents, suicides and drug abuse/overdoses. RESULTS: Compared with a sibling born in week 37-41, preterm siblings born before 34 weeks gestation had 50% increased mortality from all causes (adjusted Hazard Ratio (aHR) 1.54, 95% confidence interval (CI) 1.17, 2.03). The corresponding estimate for the entire population was 1.27 (95% CI 1.09, 1.47). The majority of deaths (65%) were from external causes and the corresponding risk estimates for these deaths were 1.52 (95% CI 1.08, 2.14) in the sibships and 1.20 (95% CI 1.01, 1.43) in the population. CONCLUSION: Preterm birth before week 34 was associated with increased mortality between 15 and 45 years of age. The results suggest that increased premature adult mortality in this group is related to external causes of death and that the increased risks are unlikely to be explained by factors shared by siblings.

Health and unemployment: 14 years of follow-up on job loss in the Norwegian HUNT Study.

BACKGROUND: Many studies have investigated how unemployment influences health, less attention has been paid to the reverse causal direction; how health may influence the risk of becoming unemployed. We prospectively investigated a wide range of health measures and subsequent risk of unemployment during 14 years of follow-up. METHODS: Self-reported health data from 36 249 participants in the Norwegian HUNT2 Study (1995-1997) was linked by a personal identification number to the National Insurance Database (1992-2008). Exact dates of unemployment were available. Cox's proportional hazard models were used to estimate hazard ratios (HR) for the association of unemployment with several health measures. Adjustment variables were age, gender, education, marital status, occupation, lifestyle and previous unemployment. RESULTS: Compared to reporting no conditions/symptoms, having ≥3 chronic somatic conditions (HR 1.78, 95% CI 1.46-2.17) or high symptom levels of anxiety and depression (HR 1.57, 95% CI 1.35-1.83) increased the risk of subsequent unemployment substantially. Poor self-rated health (HR 1.36, 95% CI 1.24-1.51), insomnia (HR 1.19, 95% CI 1.09-1.32), gastrointestinal symptoms (HR 1.17, 95% CI 1.08-1.26), high alcohol consumption (HR 1.17, 95% CI 0.95-1.44) and problematic use of alcohol measured by the CAGE questionnaire (HR 1.32, 95% CI 1.17-1.48) were also associated with increased risk of unemployment. CONCLUSION: People with poor mental and physical health are at increased risk of job loss. This contributes to poor health amongst the unemployed and highlights the need for policy focus on the health and welfare of out of work individuals, including support preparing them for re-employment.

Effect of Smoking on Blood Pressure and Resting Heart Rate: A Mendelian Randomization Meta-Analysis in the CARTA Consortium.

BACKGROUND: Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking to blood pressure are poorly understood. METHODS AND RESULTS: Data on 141 317 participants (62 666 never, 40 669 former, 37 982 current smokers) from 23 population-based studies were included in observational and Mendelian randomization meta-analyses of the associations of smoking status and smoking heaviness with systolic and diastolic blood pressure, hypertension, and resting heart rate. For the Mendelian randomization analyses, a genetic variant rs16969968/rs1051730 was used as a proxy for smoking heaviness in current smokers. In observational analyses, current as compared with never smoking was associated with lower systolic blood pressure and diastolic blood pressure and lower hypertension risk, but with higher resting heart rate. In observational analyses among current smokers, 1 cigarette/day higher level of smoking heaviness was associated with higher (0.21 bpm; 95% confidence interval 0.19; 0.24) resting heart rate and slightly higher diastolic blood pressure (0.05 mm Hg; 95% confidence interval 0.02; 0.08) and systolic blood pressure (0.08 mm Hg; 95% confidence interval 0.03; 0.13). However, in Mendelian randomization analyses among current smokers, although each smoking increasing allele of rs16969968/rs1051730 was associated with higher resting heart rate (0.36 bpm/allele; 95% confidence interval 0.18; 0.54), there was no strong association with diastolic blood pressure, systolic blood pressure, or hypertension. This would suggest a 7 bpm higher heart rate in those who smoke 20 cigarettes/day. CONCLUSIONS: This Mendelian randomization meta-analysis supports a causal association of smoking heaviness with higher level of resting heart rate, but not with blood pressure. These findings suggest that part of the cardiovascular risk of smoking may operate through increasing resting heart rate.

Heavier smoking may lead to a relative increase in waist circumference: evidence for a causal relationship from a Mendelian randomisation meta-analysis. The CARTA consortium.

OBJECTIVES: To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity. DESIGN: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730 in the CHRNA5-CHRNA3-CHRNB4 gene region) as a proxy for smoking heaviness, of the associations of smoking heaviness with a range of adiposity phenotypes. PARTICIPANTS: 148,731 current, former and never-smokers of European ancestry aged ≥ 16 years from 29 studies in the consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA). PRIMARY OUTCOME MEASURES: Waist and hip circumferences, and waist-hip ratio. RESULTS: The data included up to 66,809 never-smokers, 43,009 former smokers and 38,913 current daily cigarette smokers. Among current smokers, for each extra minor allele, the geometric mean was lower for waist circumference by -0.40% (95% CI -0.57% to -0.22%), with effects on hip circumference, waist-hip ratio and body mass index (BMI) being -0.31% (95% CI -0.42% to -0.19), -0.08% (-0.19% to 0.03%) and -0.74% (-0.96% to -0.51%), respectively. In contrast, among never-smokers, these effects were higher by 0.23% (0.09% to 0.36%), 0.17% (0.08% to 0.26%), 0.07% (-0.01% to 0.15%) and 0.35% (0.18% to 0.52%), respectively. When adjusting the three central adiposity measures for BMI, the effects among current smokers changed direction and were higher by 0.14% (0.05% to 0.22%) for waist circumference, 0.02% (-0.05% to 0.08%) for hip circumference and 0.10% (0.02% to 0.19%) for waist-hip ratio, for each extra minor allele. CONCLUSIONS: For a given BMI, a gene variant associated with increased cigarette consumption was associated with increased waist circumference. Smoking in an effort to control weight may lead to accumulation of central adiposity.

Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.

We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI) per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00 × 10(-10)), but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38 × 10(-5)). An interaction test confirmed that these estimates differed from each other (P = 4.95 × 10(-13)). This difference in effects suggests the variant influences BMI both via pathways unrelated to smoking, and via the weight-reducing effects of smoking. It would therefore be essentially undetectable in an unstratified genome-wide association study of BMI, given the opposite association with BMI in never and current smokers. This demonstrates that novel associations may be obscured by hidden population sub-structure. Stratification on well-characterized environmental factors known to impact on health outcomes may therefore reveal novel genetic associations.

Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium.

OBJECTIVES: To investigate whether associations of smoking with depression and anxiety are likely to be causal, using a Mendelian randomisation approach. DESIGN: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730) as a proxy for smoking heaviness, and observational meta-analyses of the associations of smoking status and smoking heaviness with depression, anxiety and psychological distress. PARTICIPANTS: Current, former and never smokers of European ancestry aged ≥16 years from 25 studies in the Consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA). PRIMARY OUTCOME MEASURES: Binary definitions of depression, anxiety and psychological distress assessed by clinical interview, symptom scales or self-reported recall of clinician diagnosis. RESULTS: The analytic sample included up to 58 176 never smokers, 37 428 former smokers and 32 028 current smokers (total N=127 632). In observational analyses, current smokers had 1.85 times greater odds of depression (95% CI 1.65 to 2.07), 1.71 times greater odds of anxiety (95% CI 1.54 to 1.90) and 1.69 times greater odds of psychological distress (95% CI 1.56 to 1.83) than never smokers. Former smokers also had greater odds of depression, anxiety and psychological distress than never smokers. There was evidence for positive associations of smoking heaviness with depression, anxiety and psychological distress (ORs per cigarette per day: 1.03 (95% CI 1.02 to 1.04), 1.03 (95% CI 1.02 to 1.04) and 1.02 (95% CI 1.02 to 1.03) respectively). In Mendelian randomisation analyses, there was no strong evidence that the minor allele of rs16969968/rs1051730 was associated with depression (OR=1.00, 95% CI 0.95 to 1.05), anxiety (OR=1.02, 95% CI 0.97 to 1.07) or psychological distress (OR=1.02, 95% CI 0.98 to 1.06) in current smokers. Results were similar for former smokers. CONCLUSIONS: Findings from Mendelian randomisation analyses do not support a causal role of smoking heaviness in the development of depression and anxiety.

Prevalence and long-term predictors of persistent chronic widespread pain in the general population in an 11-year prospective study: the HUNT study.

BACKGROUND: Chronic widespread pain (CWP) is common and associated with prominent negative consequences. The aim of this study was to assess the prevalence of persistent CWP in an 11-year prospective cohort study in the general population, and to examine anxiety, depression, alcohol use, poor sleep, body mass index (BMI) and chronic disease, along with demographic, lifestyle and other health-related variables as possible predictors for the assumed CWP persistence. METHODS: CWP was defined as having pain at three or more predefined sites (involving the trunk and upper and lower limbs) for at least three months in the last year. We used a Norwegian general population cohort of 28,367 individuals who responded to both the second (1995-1997) and the third (2006-2008) waves of the Nord-Trøndelag Health Study (HUNT2 and HUNT3, respectively). Data were analysed with logistic regression models. RESULTS: CWP prevalence in HUNT2 was 17%. Of those reporting CWP in HUNT2, 53% still reported CWP at follow-up in HUNT3. Adjusted analyses revealed that depression and alcohol consumption were not substantially associated with the 11-year prospective CWP outcome. Poor sleep, obesity and chronic disease predicted persistent CWP, and being male and/or 60 years or older was protective. CONCLUSIONS: This cohort study revealed that nearly half of the participants with baseline CWP resolved from CWP 11 years later. Among those whose CWP did not resolve, obesity, sleeping problems and chronic disease predicted CWP persistence, while aging and male sex was protective. Anxiety, mixed anxiety and depression, former smoking, and overweight were weakly associated, while depression, moderate exercise, and alcohol use were not associated with persistent CWP.

Psychosocial factors and risk of chronic widespread pain: an 11-year follow-up study--the HUNT study.

Few studies have used prospective designs in large population surveys to assess the risk of developing chronic widespread pain (CWP). We wanted to examine 1) how many people without CWP developed it after 11years, and 2) how anxiety, depression, alcohol use, smoking, sleeping problems, and body mass index (BMI) were associated with this development. This study was based on a representative population-based Norwegian cohort attending both the second (1995 to 1997) and the third (2006 to 2008) wave of the Nord-Trøndelag Health Study (HUNT2 and HUNT3, respectively). Only those adults attending both surveys (N=28,367) were included. Approximately 19,000 individuals without CWP in HUNT2 were assessed for later CWP development in HUNT3, where we looked for symptoms of anxiety, depression, monthly frequency of alcohol use, smoking, sleeping problems, and BMI. Data were analyzed with logistic regression adjusted for age, sex, education, marital status, physical exercise, and pain symptoms not meeting the CWP criteria at baseline. After 11 years, 12% of those without CWP developed CWP. Anxiety and depression, former and current smoking status, BMI<18.5 kg/m(2), BMI⩾25 kg/m(2), and sleeping problems were all associated with an increased risk of CWP. High and moderate levels of alcohol use were associated with a reduced risk of CWP. In summary, this study indicates that CWP develops over a long-term period for a substantial group of healthy people, and that both psychosocial and lifestyle factors influence the risk of CWP onset.

Causal associations of tobacco smoking with cardiovascular risk factors: a Mendelian randomization analysis of the HUNT Study in Norway.

BACKGROUND: Tobacco smoking has been associated with cardiovascular risk factors including adverse serum lipid levels, central obesity and higher resting heart rate, but lower blood pressure and body mass index (BMI). We used a Mendelian randomization approach to study whether these associations may be causal. If smoking affects cardiovascular risk factors then rs1051730 T alleles, predictors of increased smoking quantity, should be associated with cardiovascular risk factors among smokers, but not among never smokers. METHODS: Among 56,625 participants of a population-based study, we estimated associations of rs1051730 T alleles with cardiovascular risk factors and examined whether the associations differed by smoking status. RESULTS: Rs1051730 T alleles were associated with lower BMI and waist and hip circumferences and higher resting heart rate and estimated glomerular filtration rate (eGFR), and the associations were strongest among current smokers (P interaction 5×10(-9) to 0.01). Rs1051730 T alleles were associated with lower systolic blood pressure and pulse pressure and higher HDL cholesterol concentrations, but these associations did not robustly differ by smoking status. There were no convincing associations of rs1051730 T alleles with waist-hip ratio, diastolic blood pressure and non-fasting serum concentrations of non-HDL cholesterol, triglycerides, glucose and C-reactive protein. CONCLUSIONS: This Mendelian randomization analysis provides evidence that smoking may cause lower BMI and waist and hip circumferences and higher resting heart rate and eGFR. The findings further suggest that smoking is not a major determinant of waist-hip ratio or adverse blood pressure, serum lipid or glucose levels.

Unemployment and disability pension--an 18-year follow-up study of a 40-year-old population in a Norwegian county.

BACKGROUND: This study explored the association of unemployment and an increased risk of receiving disability pension, and the possibility that this risk is attributed to municipality-specific characteristics. METHODS: A cohort of 7,985 40-42 year olds was followed for 18 years in national registers, identifying new episodes of unemployment and cases of disability pension. The association between an unemployment period and disability pension in the subsequent year was estimated using discrete time multilevel logistic regressions and clustering individuals by municipality. The association between unemployment and disability pension was adjusted for age in the follow up-period, sex, baseline health status, health behaviour and education level. A conditional intra-class correlation coefficient (ICC) was estimated as a measure of inter-municipality variance. RESULTS: In the follow-up period, 2784 (35%) of the participants were granted disability pension. The crude odds ratio for receiving disability pension after unemployment (adjusted for age in follow-up period and sex only) was 1.42 (95% CI 1.1-1.8). Adjusting for baseline health indicators reduced the odds ratio of unemployment to 1.33 (CI 1.1-1.7). A fully adjusted model, including education level, further reduced the odds ratio of unemployment to 1.25 (CI 1.00-1.6). The ICC of the municipality level was approximately 2%. CONCLUSIONS: Becoming unemployed increased the risk of receiving subsequent disability pension. However, adjusting for baseline health status, health behaviour and education attenuated this impact considerably. The multilevel analysis indicated that a minor, yet statistically significant, proportion of the risk of disability pension can be attributed to the municipality of residence.