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Background: Psoriasis is associated with high alcohol consumption, but the causality of this relationship is unclear. Objective: We aimed to use a Mendelian randomization approach to investigate the causal effects of alcohol on incident psoriasis. Methods: We included 102,655 adults from the prospective Copenhagen studies. All participants filled out a questionnaire on alcohol consumption, were physically examined, and had blood drawn for biochemical and genetic analyses. We created a genetic instrument based on the number of fast-metabolizing alleles in alcohol dehydrogenase 1B and alcohol dehydrogenase 1C, known to be associated with alcohol consumption, to test whether alcohol consumption was causally associated with psoriasis. Results: Observationally, we found an increased risk of incident psoriasis among individuals with high alcohol consumption compared to those with low alcohol consumption with a hazard ratio of 1.30 (95% confidence interval 1.05-1.60) in the fully adjusted model. Using genetic data to predict alcohol consumption to avoid confounding and reverse causation, we found no association between number of fast-metabolizing alleles and risk of psoriasis. Limitations: Alcohol consumption was self-reported and psoriasis was defined using the International Classification of Diseases 10th revision and 8th revision codes. Conclusion: Alcohol consumption is observationally but not causally associated with incident psoriasis.

Abstract Background The individual woman’s risk of being diagnosed with breast cancer can now be estimated more precisely, and screening can be stratified accordingly. The risk assessment requires that women are willing to provide a blood test, additional personal information, to know their risk, and alter screening intervals. This study aimed to investigate Danish women’s attitudes towards risk-stratified breast cancer screening. Methods An online, cross-sectional survey was conducted among Danish women aged 52–67 years. We used logistic regression analyses to assess how personal characteristics were associated with the women’s attitudes. Results 5,001 women completed the survey (response rate 44%) of which 74% approved of risk estimation to potentially alter their screening intervals. However, only 42% would accept an extended screening interval if found to have low breast cancer risk, while 89% would accept a reduced interval if at high risk. The main determinants of these attitudes were age, education, screening participation, history of breast cancer, perceived breast cancer risk and to some extent breast cancer worry. Conclusion This study indicates that women are positive towards risk-stratified breast cancer screening. However, reservations and knowledge among subgroups of women must be carefully considered and addressed before wider implementation of risk-stratified breast cancer screening in a national program.

Objectives: The aim was to determine the association between self-reported health (SRH), allostatic load (AL) and mortality.Methods: Data derived from the Lolland-Falster Health Study undertaken in Denmark from 2016–2020 (n = 14,104). Median follow-up time for death was 4.6 years where 456 participants died. SRH was assessed with a single question and AL by an index of ten biomarkers. Multinomial regression analysis were used to examine the association between SRH and AL, and Cox regression to explore the association between SRH, AL and mortality.Results: The risk of high AL increased by decreasing level of SRH. The ratio of relative risk (RRR) of having medium vs. low AL was 1.58 (1.11–2.23) in women reporting poor/very poor SRH as compared with very good SRH. For men it was 1.84 (1.20–2.81). For high vs. low AL, the RRR was 2.43 (1.66–3.56) in women and 2.96 (1.87–4.70) in men. The hazard ratio (HR) for all-cause mortality increased by decreasing SRH. For poor/very poor vs. very good SRH, the HR was 6.31 (2.84–13.99) in women and 3.92 (2.12–7.25) in men.Conclusion: Single-item SRH was able to predict risk of high AL and all-cause mortality.

BackgroundSmoking is strongly associated with higher risk of psoriasis in several observational studies; however, whether this association is causal or can be explained by confounding or reverse causation is not fully understood. Randomized controlled trials are the gold standard when examining causality; however, when this method is not feasible, the Mendelian randomization design is an alternative. Herein genetic variants can be used as robust proxies for modifiable exposures and thereby avoiding confounding and reverse causation.In this study, we hypothesized that smoking is an independent and causal risk factor for psoriasis and tested this using a Mendelian randomization design.MethodsWe used data from the Copenhagen General Population Study including 105,912 individuals with full information on lifestyle factors, biochemistry, and genotype data. In total, 1,240 cases of moderate to severe psoriasis were included to investigate the association between smoking and psoriasis. To assess causality of the association, we used the genetic variant CHRNA3 rs1051730, where the T-allele is strongly associated with high lifelong cumulative smoking, as a proxy for smoking.ResultsIn observational analyses, the multivariable adjusted hazard ratio of developing moderate to severe psoriasis was 1.64 (95% confidence interval: 1.35-2.00) in ever smokers with ≤ 20 pack-years and 2.23 (1.82-2.73) in ever smokers with > 20 pack-years compared to never smokers. In genetic analyses, the odds ratio of developing moderate to severe psoriasis was 1.05 (0.95-1.16) per CHRNA3 rs10511730 T-allele in ever smokers.ConclusionSmoking was an independent risk factor for moderate to severe psoriasis in observational analyses. However, using a genetic variant as a robust proxy for smoking, we did not find this association to be causal.

BackgroundPsoriasis is observationally associated with a higher risk of non-alcoholic fatty liver disease (NAFLD); however, the causal relationship between the two diseases remains unclear.ObjectiveWe hypothesized that individuals with NAFLD or elevated liver fat content have higher risk of psoriasis and that NAFLD is a causal risk factor for psoriasis. We tested this using a Mendelian randomization approach.MethodsWe included 108,835 individuals from the Danish general population, including 1,277 individuals with psoriasis and 802 individuals with NAFLD according to ICD codes. To estimate liver fat content, a subset of the participants (N = 7,416) also had a CT scan performed. First, we tested whether a diagnosis of NAFLD or elevated liver fat content was observationally associated with risk of psoriasis. Subsequently, we used the genetic variants PNPLA3 and TM6SF2, both strongly associated with NAFLD and high liver fat content, to test whether NAFLD was causally associated with increased risk of psoriasis.ResultsObservationally, individuals with vs. without a diagnosis of NAFLD had higher risk of psoriasis with an odds ratio of 2.03 (95% confidence interval 1.28-3.21). The risk of psoriasis increased in a stepwise manner with increasing liver fat content with an odds ratio of 5.00 (2.63-9.46) in individuals in the highest quartile of liver fat content compared to individuals in the lowest quartile. In genetic analyses, PNPLA3 and TM6SF2 were both associated with increased risk of NAFLD but not with increased risk of psoriasis.ConclusionObservationally, a diagnosis of NAFLD or elevated liver fat content was associated with higher risk of psoriasis. However, using genetic variants as a proxy for NAFLD, we did not find evidence of a causal relationship between NAFLD and psoriasis. Thus, the observational association between NAFLD and psoriasis is presumably a result of shared confounding factors or reverse causation.

Women with cardiovascular disease are underdiagnos-ed, undertreated and under-represented in research. Even though the increased risk of cardiovascular disease among patients with psoriasis is well establi-shed, only a few studies have examined women with psoriasis. This study examined the prevalence of cardio-vascular risk factors and cardiovascular disease among women with psoriasis. Using the Copenhagen City Heart Study and the Copenhagen General Population Study, 66,420 women were included in a cross-sectional design. Of these, 374 (0.56%) women had hospital-diagnosed psoriasis. Women with vs with-out hospital-diagnosed psoriasis had higher odds ratios of having traditional cardiovascular risk factors, including hypertriglyceridaemia, smoking, obesity, type 2 diabetes, and low physical activity, and of having non-traditional cardiovascular risk factors, including low level of education, high level of psycho-social stress, and low-grade inflammation. Compared with women from the general population, the multi-variable adjusted odds ratio of heart failure and ischaemic cerebrovascular disease in women with hospital-diagnosed psoriasis was 2.51 (95% confidence interval 1.33–4.73) and 2.06 (1.27–3.35). In conclusion, women with hospital-diagnosed psoriasis have a higher prevalence of traditional and non- traditional cardiovascular risk factors, and increased risk of heart failure and ischaemic cerebrovascular disease, even after adjusting for these cardiovascular risk factors.

Objectives The purposes of the present study were to determine the association between (1) 10 individual biomarkers and all-cause mortality; and between (2) allostatic load (AL), across three physiological systems (cardiovascular, inflammatory, metabolic) and all-cause mortality.Design Prospective cohort study.Setting We used data from the Lolland-Falster Health Study undertaken in Denmark in 2016–2020 and used data on systolic blood pressure (SBP) and diastolic blood pressure (DBP), pulse rate (PR), waist–hip ratio (WHR) and levels of low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), triglycerides, glycated haemoglobin A1c (HbA1c), C-reactive protein (CRP) and serum albumin. All biomarkers were divided into quartiles with high-risk values defined as those in the highest (PR, WHR, triglycerides, HbA1c, CRP) or lowest (HDL-c, albumin) quartile, or a combination hereof (LDL-c, SBP, DBP). The 10 biomarkers were combined into a summary measure of AL index. Participants were followed-up for death for an average of 2.6 years.Participants We examined a total of 13 725 individuals aged 18+ years.Primary outcome measure Cox proportional hazard regression (HR) analysis were performed to examine the association between AL index and mortality in men and women.Results All-cause mortality increased with increasing AL index. With low AL index as reference, the HR was 1.33 (95% CI: 0.89 to 1.98) for mid AL, and HR 2.37 (95% CI: 1.58 to 3.54) for high AL.Conclusions Elevated physiological burden measured by mid and high AL index was associated with a steeper increase of mortality than individual biomarkers.

Abstract Background This study aimed to investigate prevalence and risk factors for prediabetes, undiagnosed diabetes mellitus, poorly and potentially sub-controlled diabetes in a rural-provincial general adult population in Denmark. Methods Using cross-sectional data from the Lolland-Falster Health Study, we examined a total of 10,895 individuals aged 20 years and above. Results Prevalence of prediabetes was 5.8% (men: 6.1%; women: 5.5%); of undiagnosed diabetes 0.8% (men: 1.0%; women: 0.5%); of poorly controlled diabetes 1.2% (men: 1.5%; women: 0.8%); and of potentially sub-controlled diabetes 2% (men: 3.0%; women: 1.3%). In total, 9.8% of all participants had a diabetes-related condition in need of intervention; men at a higher risk than women; RR 1.41 (95% CI 1.26–1.58); person aged + 60 years more than younger; RR 2.66 (95% CI 2.34–3.01); obese more than normal weight person, RR 4.51 (95% CI 3.79–5.38); smokers more than non-smokers, RR 1.38 (95% CI 1.19–1.62); persons with self-reported poor health perception more than those with good, RR 2.59 (95% CI 2.13–3.15); low leisure time physical activity more than those with high, RR 2.64 (95% CI 2.17–3.22); and persons with self-reported hypertension more than those without, RR 3.28 (95% CI 2.93–3.68). Conclusions In the Lolland-Falster Health Study, nearly 10% of participants had prediabetes, undiagnosed diabetes, poorly controlled, or potentially sub-controlled diabetes. The risk of these conditions was more than doubled in persons with self-reported poor health perception, self-reported hypertension, low leisure time physical activity, or measured obesity, and a large proportion of people with diabetes-related conditions in need of intervention can therefore be identified relatively easily.

Abstract Background Increasing evidence suggests that high-density lipoprotein (HDL) may play a role in cancer development. We tested the hypothesis that low HDL levels are associated with increased risk of cancer. Methods Individuals from two population-based cohorts, the Copenhagen General Population Study (2003–2015, N = 107 341), and the Copenhagen City Heart Study (1991–1994, N = 9387) were followed prospectively until end of 2016 to assess low plasma HDL cholesterol and apolipoprotein A1 as risk factors for cancer using Cox proportional hazard regression. Results During up to 25 years follow-up, we observed 8748 cancers in the Copenhagen General Population Study and 2164 in the Copenhagen City Heart Study. In the Copenhagen General Population Study and compared to individuals with HDL cholesterol ≥ 2.0 mmol/L (≥ 77 mg/dL), multivariable adjusted hazard ratios (HRs) for any cancer were 1.13 (95% confidence interval 1.04–1.22) for individuals with HDL cholesterol of 1.5–1.99 mmol/L (58–77 mg/dL), 1.18 (1.08–1.30) for HDL cholesterol of 1.0–1.49 mmol/L (39–58 mg/dL), and 1.29 (1.12–1.48) for individuals with HDL cholesterol < 1.0 mmol/L (< 39 mg/dL). Correspondingly, compared to individuals with apolipoprotein A1 ≥ 190 mg/dL, HRs for any cancer were 1.06 (0.96–1.17) for individuals with apolipoprotein A1 of 160–189 mg/dL, 1.18 (1.07–1.30) for apolipoprotein A1 of 130–159 mg/dL, and 1.28 (1.13–1.46) for individuals with apolipoprotein A1 < 130 mg/dL. Among 27 cancer types, low HDL cholesterol and/or apolipoprotein A1 were associated with increased risk of multiple myeloma, myeloproliferative neoplasm, non-Hodgkin lymphoma, breast cancer, lung cancer, and nervous system cancer. Results were overall similar in women and men separately, and in the Copenhagen City Heart Study. Conclusions Low HDL levels were associated with increased risk of several cancers. Increased risk was most pronounced for hematological and nervous system cancer, and to a minor extent for breast and respiratory cancer.

Background: Whether inflammation is independently associated with development of JAK2V617F mutation and myeloproliferative neoplasm is not clear. We tested the hypothesis that a loss-of-function polymorphism in IL6R (marked by rs4537545) reduces risk of JAK2V617F mutation and myeloproliferative neoplasm in a Mendelian randomization study. Methods: We genotyped 107,969 Danes from the Copenhagen General Population Study for the IL6R rs4537545 genotype, where the T-allele is associated with impaired interleukin-6 receptor signaling and reduced inflammation. JAK2V617F was examined in a subset of 49,143 individuals. We investigated the association between IL6R rs4537545 and risk of JAK2V617F using logistic regression and myeloproliferative neoplasm using Cox regression. Findings: 36,871 were non-carriers, 52,500 heterozygotes, and 18,598 homozygotes for the T-allele of the IL6R rs4537545 genotype. Among 107,969 individuals, 352 were diagnosed with myeloproliferative neoplasm, and among 49,143 individuals, 62 were JAK2V617F-positive (of these 62 individuals, 46 had myeloproliferative neoplasm diagnosed). Compared to non-carriers, age- and sex-adjusted odds ratios for risk of JAK2V617F were 0·55(95%CI:0·32–0·94) in heterozygotes, 0·51(0·24–1·12) in homozygotes, 0·54(0·33–0·89) in carriers, and 0·66(0·45–0·96) per T-allele. Compared to non-carriers, age- and sex-adjusted hazard ratios for risk of myeloproliferative neoplasm were 0·82(95% CI: 0·65–1·02) in heterozygotes, 0·65(0·47–0·91) in homozygotes, 0·77(0·63–0·96) in carriers, and 0·81(0·70–0·94) per T-allele. Associations were primarily observed for polycythaemia vera and myelofibrosis, and for JAK2V617F-positive myeloproliferative neoplasm. Interpretation: A loss-of-function polymorphism in IL6R reduces risk of JAK2V617F mutation and myeloproliferative neoplasm. This finding supports inflammation as an independent risk factor for JAK2V617F mutation and myeloproliferative neoplasm and indicates that therapeutics designed to block interleukin-6 receptor signaling might prevent or retard progression of myeloproliferative neoplasm. Funding: Karen Elise Jensen Foundation. Keywords: Mendelian randomization, Myeloproliferative neoplasm, Essential thrombocythemia, Polycythemia vera, Myelofibrosis, Drug target

Background: High cardiovascular comorbidity contributes to excess mortality in patients with myeloproliferative neoplasm, while less is known about respiratory comorbidity and mortality. We tested the hypothesis that individuals with myeloproliferative neoplasm have increased risk of pneumonia and respiratory mortality. Methods: Of 249 294 invited individuals aged ≥20 from the Danish general population from 2003–2015, 107 900 participated and were included in the Copenhagen General Population Study (response-rate: 43%). We examined lung function and respiratory symptoms at baseline examination and followed individuals prospectively from baseline examination through 2018 to determine risk of pneumonia and respiratory mortality using Cox proportional hazard regression. Among 351 individuals with myeloproliferative neoplasm, 131 (37%) were diagnosed at baseline examination and 220 (63%) were diagnosed during follow-up. The follow-up cases were entered in the regression analysis by using a time-varying variable. Findings: In total, 125 (36%) individuals had essential thrombocythaemia, 124 (35%) had polycythaemia vera, and 102 (29%) had myelofibrosis/unclassifiable myeloproliferative neoplasm. During follow-up we observed 5979 pneumonias and 2278 respiratory deaths. Compared to individuals without myeloproliferative neoplasm, multivariable adjusted hazard ratios in individuals with myeloproliferative neoplasm were 2·18 (95% CI: 1·60-2·96) for pneumonia and 2·27 (1·46-3·53) for respiratory mortality. Corresponding hazard ratios were 1·26 (0·71-2·30) and 0·96 (0·31-2·94) for essential thrombocythaemia, 2·50 (1·57-3·98) and 3·58 (1·94-6·59) for polycythaemia vera, and 3·03 (1·86-4·93) and 2·40 (1·11-5·19) for myelofibrosis/unclassifiable myeloproliferative neoplasm, respectively. Results were similar in those with and without airflow limitation, and in never-smokers and ever-smokers separately. Interpretation: Individuals with myeloproliferative neoplasm had two-fold increased risk of pneumonia and respiratory mortality, mainly due to polycythaemia vera and myelofibrosis/unclassifiable myeloproliferative neoplasm. These are novel findings.

Abstract Lung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB1*0401 and HLA-DRB1*0701; the latter better represented by the amino acid Ala-104. These results implicate several HLA–tumor peptide interactions as the major MHC factor modulating lung cancer susceptibility.

Introduction We examined changes in smoking habits in the general population according to prevalence and incidence of chronic diseases affected by smoking. Methods We included 12283 individuals enrolled from 2003 in the Copenhagen General Population Study and re-examined from 2014. Participants were classified as either healthy or suffering from chronic obstructive pulmonary disease (COPD), asthma, diabetes mellitus, heart disease or stroke. Results At entry, smoking prevalence was 15.4% in healthy participants, 29.8% with COPD, 15.8% with asthma, 21.7 % with diabetes mellitus, 17.2 % with ischemic heart disease/heart failure and 18.6% in participants with previous stroke. Smoking prevalence declined during the 10 years of observation. Among healthy subjects who developed one of the above mentioned diseases during follow-up, those who developed COPD had the highest initial smoking prevalence (51.5%). Quit rates were highest in those who developed asthma resulting in smoking prevalence of 8.2% versus 27.7% in COPD. After adjustment for age, smoking severity and genotype previously associated with heavy smoking (CHRNA3 rs1051730 AA), significant predictors of quitting were new diagnosis of ischemic heart disease/heart failure (OR=2.33, 95 % CI: 1.61–3.42), new diagnosis of asthma (OR=1.84, 95% CI: 1.18–2.90) and low number of pack-years. Conclusions Individuals with prevalent smoking related diseases continued to smoke more than healthy individuals. Incident heart disease and asthma, but not incident COPD, stroke or diabetes were associated with a higher chance of quitting. Special focus on smokers with COPD, asthma, diabetes, stroke and ischemic heart disease/heart failure is warranted to decrease smoking prevalence in these groups. Smokers with a new diagnosis of diabetes, stroke and COPD need special smoking cessation support.

BackgroundWhile physical activity reduces risk of developing myocardial infarction (MI), it is unknown whether a history of physical activity is also protective of fatal arrhythmia and case-fatality in patients who have suffered an acute MI.Methods104,801 individuals included in 2003-2014 in the Copenhagen General Population Study (CGPS), a prospective population-based study with self-reported leisure time physical activity (LTPA) in three categories measured at baseline, were followed until 2014 through national registries. The 1,517 individuals who suffered a first time MI during follow-up constituted the study population. Outcomes were fatal MI, defined as date of death same as date of MI (including out-of-hospital deaths) and 28-day fatality. Through multivariable analyses the association between baseline LTPA and outcomes were assessed adjusted for CVD risk factors.ResultsOf 1,517 MI events, 117 (7.7%) were fatal and another 79 (5.6%) lead to death within 28 days. Median time from baseline to MI was 3.6 years (IQR 1.7-5.8). LTPA was associated with lower risk of fatal MI with odds ratios of 0.40 (95% CI: 0.22-0.73) for light and 0.41 (0.22-0.76) for moderate/high LTPA after multivariable adjustment with sedentary LTPA as reference. Age, alcohol-intake, education and smoking were identified as other predictors for fatal MI. We found no association between LTPA and 28-day case fatality.ConclusionsAmong individuals with MI, those that have engaged in any light or moderate physical activity were more likely to survive their MI. Results are consistent with effect of exercise preconditioning on risk of fatal arrhythmia.

BackgroundPrior studies have shown that AHRR (cg05575921) hypomethylation may be a marker of smoking, lung cancer risk and potentially lung cancer survival (in some lung cancer subtypes). It is unknown if AHRR (cg05575921) hypomethylation is associated with reduced survival among lung cancer patients.MethodsIn bisulfite treated leukocyte DNA from 465 lung cancer patients from the Copenhagen prospective lung cancer study, we measured AHRR (cg05575921) methylation. 380 died during max follow-up of 4.4 years. Cox proportional hazard models were used to analyze survival as a function of AHRR (cg05575921) methylation.ResultsWe observed the expected inverse correlation between cumulative smoking and AHRR methylation, as methylation (%) decreased (Coefficient -0.03; 95% confidence interval, -0.04- -0.02, p = 8.6x10-15) for every pack-year. Cumulative smoking > 60 pack-years was associated with reduced survival (hazard ratio and 95% confidence interval 1.48; 1.05-2.09), however, AHRR (cg05575921) methylation was not associated with survival when adjusted for sex, body mass index, smoking status, ethnicity, performance status, TNM Classification, and histology type of lung cancer.ConclusionAHRR (cg05575921) methylation is linked to smoking but does not provide independent prognostic information in lung cancer patients.

BACKGROUND:Neutropenia increases the risk of infection, but it is unknown if this also applies to lymphopenia. We therefore tested the hypotheses that lymphopenia is associated with increased risk of infection and infection-related death in the general population. METHODS AND FINDINGS:Of the invited 220,424 individuals, 99,191 attended examination. We analyzed 98,344 individuals from the Copenhagen General Population Study (Denmark), examined from November 25, 2003, to July 9, 2013, and with available blood lymphocyte count at date of examination. During a median of 6 years of follow-up, they developed 8,401 infections and experienced 1,045 infection-related deaths. Due to the completeness of the Danish civil and health registries, none of the 98,344 individuals were lost to follow-up, and those emigrating (n = 385) or dying (n = 5,636) had their follow-up truncated at the day of emigration or death. At date of examination, mean age was 58 years, and 44,181 (44.9%) were men. Individuals with lymphopenia (lymphocyte count < 1.1 × 109/l, n = 2,352) compared to those with lymphocytes in the reference range (1.1-3.7 × 109/l, n = 93,538) had multivariable-adjusted hazard ratios of 1.41 (95% CI 1.28-1.56) for any infection, 1.31 (1.14-1.52) for pneumonia, 1.44 (1.15-1.79) for skin infection, 1.26 (1.02-1.56) for urinary tract infection, 1.51 (1.21-1.89) for sepsis, 1.38 (1.01-1.88) for diarrheal disease, 2.15 (1.16-3.98) for endocarditis, and 2.26 (1.21-4.24) for other infections. The corresponding hazard ratio for infection-related death was 1.70 (95% CI 1.37-2.10). Analyses were adjusted for age, sex, smoking status, cumulative smoking, alcohol intake, body mass index, plasma C-reactive protein, blood neutrophil count, recent infection, Charlson comorbidity index, autoimmune diseases, medication use, and immunodeficiency/hematologic disease. The findings were robust in all stratified analyses and also when including only events later than 2 years after first examination. However, due to the observational design, the study cannot address questions of causality, and our analyses might theoretically have been affected by residual confounding and reverse causation. In principle, fluctuating lymphocyte counts over time might also have influenced analyses, but lymphocyte counts in 5,181 individuals measured 10 years after first examination showed a regression dilution ratio of 0.68. CONCLUSIONS:Lymphopenia was associated with increased risk of hospitalization with infection and increased risk of infection-related death in the general population. Notably, causality cannot be deduced from our data.

Background: Depression has been cross-sectionally associated with short telomeres as a measure of biological age. However, the direction and nature of the association is currently unclear., Aims: We examined whether short telomere length is associated with depression cross-sectionally as well as prospectively and genetically., Method: Telomere length and three polymorphisms, TERT, TERC and OBFC1, were measured in 67 306 individuals aged 20-100 years from the Danish general population and associated with register-based attendance at hospital for depression and purchase of antidepressant medication., Results: Attendance at hospital for depression was associated with short telomere length cross-sectionally, but not prospectively. Further, purchase of antidepressant medication was not associated with short telomere length cross-sectionally or prospectively. Mean follow-up was 7.6 years (range 0.0-21.5). The genetic analyses suggested that telomere length was not causally associated with attendance at hospital for depression or with purchase of antidepressant medication., Conclusions: Short telomeres were not associated with depression in prospective or in causal, genetic analyses., (© The Royal College of Psychiatrists 2017.)