Tea Skaaby

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.

Vitamin D Status and Changes in Cardiovascular Risk Factors: A Prospective Study of a General Population

Objectives: A low vitamin D level has been associated with increased cardiovascular disease risk but possible mechanisms remain unclear. We investigated the association between vitamin D levels and 5-year changes in blood pressure, lipid profile and incidence of the metabolic syndrome, hypertension and hypercholesterolemia. Methods: A random sample of 6,784 individuals aged 30–60 years from a general population was investigated in the Inter99 study in 1999–2001. Vitamin D (serum 25-hydroxyvitamin D) was measured at baseline by high-performance liquid chromatography, and 4,330 individuals participated at the 5-year follow-up and were included in the present study. Results: The median baseline vitamin D concentration was 48.0 nmol/l. In multivariable linear regression analyses, a 10 nmol/l higher baseline level of vitamin D was associated with a decrease in triglycerides and very low density lipoprotein cholesterol by 0.52 (p = 0.03) and 0.66% (p = 0.005), respectively. In multivariable logistic regression analyses, the odds ratios per 10 nmol/l higher baseline vitamin D level were 0.95 (p < 0.05) and 0.94 (p = 0.01) for the development of the metabolic syndrome and hypercholesterolemia, respectively. There was no association between vitamin D and blood pressure. Conclusions: An optimal vitamin D status may influence cardiovascular health by changing the lipid profile in a favorable direction and decreasing the incidence of the metabolic syndrome.

IgE antibodies to alpha‐gal in the general adult population: relationship with tick bites, atopy, and cat ownership

The carbohydrate alpha‐gal epitope is present in many animal proteins, including those of red meat and animal immunoglobulins, such as cat IgA. Systemic anaphylaxis to the alpha‐gal epitope has recently been described.

Prospective Population-Based Study of the Association between Serum 25-Hydroxyvitamin-D Levels and the Incidence of Specific Types of Cancer

Background: Observational studies have suggested an inverse association between vitamin D status and cancer. We investigated the prospective associations between vitamin D status and the total and specific type of cancer in three cohorts from the general Danish population. Methods: A total of 12,204 individuals 18 to 71 years old were included. The level of 25-hydroxyvitamin D was measured at baseline, and information about cancer was obtained from the Danish Cancer Registry. Results: During the 11.3-year median follow-up time, there were 1,248 incident cancers. HRs [95% confidence intervals (CI)] per 10 nmol/L higher baseline vitamin D level were: for all cancers (HR = 1.02; 95% CI, 0.99–1.04), all cancers excluding non-melanoma skin cancer, NMSC (HR = 1.00; 95% CI, 0.97–1.03), head and neck cancer (HR = 0.97; 95% CI, 0.84–1.12), colorectal cancer (HR = 0.95; 95% CI, 0.88–1.02), cancer of bronchus and lung (HR = 0.98; 95% CI, 0.91–1.05), breast cancer (HR = 1.02; 95% CI, 0.96–1.09), cancer of the uterus (HR = 1.10; 95% CI, 0.95–1.27), prostate cancer (HR = 1.00; 95% CI, 0.93–1.08), cancer of the urinary organs (HR = 1.01; 95% CI, 0.90–1.14), NMSC (HR = 1.06; 95% CI, 1.02–1.10), and malignant melanoma (HR = 1.06; 95% CI, 0.95–1.17). Conclusions: Apart from a significantly higher risk for NMSC with higher vitamin D status, we found no statistically significant associations between vitamin D status and total or specific cancers. Impact: Our results do not indicate that there is an impact of vitamin D on total cancer incidence. Cancer Epidemiol Biomarkers Prev; 23(7); 1220–9. ©2014 AACR.

Serum 25(OH)D and incident type 2 diabetes: a cohort study.

BACKGROUND/OBJECTIVES:Mild to moderate vitamin D insufficiency has been proposed as a risk factor for several common chronic diseases including type 2 diabetes. This study aimed to examine the association between serum 25-hydroxy vitamin D (25(OH)D) and incident diabetes.SUBJECTS/METHODS:The MONICA10 cohort consists of 2656 participants (men and women aged 41–71 years) who participated in a 10-year follow-up examination during 1993–1994 as part of the MONICA 1 population survey. A total of 2571 participants free of diabetes at baseline and with successful measurement of serum 25(OH)D were included in the current study. The Danish National Diabetes register enabled identification of 288 cases of incident diabetes during follow-up (median: 16.4 years). Data were analysed by Cox proportional hazard models and associations were expressed as hazard ratios (HRs) with 95% confidence intervals (CIs).RESULTS:Serum 25(OH)D was inversely associated with incident diabetes adjusted for potential confounders (HR per 25 nmol/l=0.83; 95% CI: 0.72–0.95; P=0.009). A statistically significant interaction was observed between 25(OH)D and waist circumference (WC) (Pinteraction=0.042) suggesting an association in persons with a high WC (HR (95%CI) per 25 nmol/l=0.74 (0.63–0.88), 218 incident cases) and not in persons with a normal WC (HR (95%CI) per 25 nmol/l=0.98 (0.78–1.24), 70 incident cases).CONCLUSIONS:Low serum 25(OH)D was associated independently with incident diabetes. The inverse association was only found in overweight-obese and not in normal weight individuals, suggesting that obesity may modify the effect of vitamin D status on the risk of diabetes.

Vitamin D status and cause-specific mortality: a general population study.

Background Vitamin D deficiency is associated with an increased risk of all-cause mortality in observational studies. The specific causes of death underlying this association lack clarity. We investigated the association between vitamin D status and cause-specific mortality. Methods We included a total of 9,146 individuals from the two population-based studies, Monica10 and Inter99, conducted in 1993–94 and 1999–2001, respectively. Vitamin D status was assessed as serum 25-hydroxyvitamin D. Information on causes of death was obtained from The Danish Register of Causes of Death until 31 December 2009. There were a total of 832 deaths (median follow-up 10.3 years). Results Multivariable Cox regression analyses with age as underlying time axis and vitamin D quartiles showed significant associations between vitamin D status and death caused by diseases of the respiratory system, the digestive system, and endocrine, nutritional and metabolic diseases with hazard ratios (HRs) 0.26 (ptrend = 0.0042), 0.28 (ptrend = 0.0040), and 0.21 (ptrend = 0.035), respectively, for the fourth vitamin D quartile compared to the first. We found non-significantly lower HRs for death caused by mental and behavioural diseases and diseases of the nervous system, but no association between vitamin D status and death caused by neoplasms or diseases of the circulatory system. Conclusion The associations of vitamin D status and cause-specific mortality suggest that we also look elsewhere (than to cardiovascular disease and cancer) to explain the inverse association between vitamin D status and mortality.

Rare genetic variants previously associated with congenital forms of long QT syndrome have little or no effect on the QT interval

AIMS We studied whether variants previously associated with congenital long QT syndrome (cLQTS) have an effect on the QTc interval in a Danish population sample. Furthermore, we assessed whether carriers of variants in cLQTS-associated genes are more prone to experience syncope compared with non-carriers and whether carriers have an increased mortality compared with non-carriers. METHODS AND RESULTS All genetic variants previously associated with cLQTS were surveyed using the Human Gene Mutation Database. We screened a Danish population-based sample with available whole-exome sequencing data (n = 870) and genotype array data (n = 6161) for putative cLQTS genetic variants. In total, 33 of 1358 variants previously reported to associate with cLQTS were identified. Of these, 10 variants were found in 8 or more individuals. Electrocardiogram results showed normal mean QTc intervals in carriers compared with non-carriers. Syncope data analysis between variant and non-variant carriers showed that 4 of 227 (1.8%) and 95 of 5861 (1.6%) individuals, respectively, had experienced syncope during follow-up (P = 0.80). There was no significant difference in overall mortality rates between carriers [7/217 (3.2%)] and non-carriers [301/6453 (4.7%)] (P = 0.24). CONCLUSION We present QTc data and register data, indicating that 26 cLQTS-associated variants neither had any effect on the QTc intervals nor on syncope propensity or overall mortality. Based on the frequency of individual gene variants, we suggest that the 10 variants frequently identified, assumed to relate to cLQTS, are less likely to associate with a dominant monogenic form of the disease.

Vitamin D Status, Filaggrin Genotype, and Cardiovascular Risk Factors: A Mendelian Randomization Approach

Background Vitamin D deficiency is associated with increased cardiovascular disease risk in observational studies. Whether these associations are causal is not clear. Loss-of-function mutations in the filaggrin gene result in up to 10% higher serum vitamin D concentrations, supposedly due to a decreased UV-protection of the keratinocytes. We used a Mendelian randomization approach to estimate the causal effect of vitamin D status on serum lipids, blood pressure, body mass index, waist circumference, and the metabolic syndrome. Methods Three population based studies were included, Monica10 (2,656 individuals aged 40–71 years), Inter99 (6,784 individuals aged 30–60 years), and Health2006 (3,471 individuals aged 18–69 years) conducted in 1993–94, 1999–2001, and 2006–2008, respectively. Participants were genotyped for the two most common filaggrin gene mutations in European descendants R501X and 2282del4, in all three studies and further for the R2447X mutation in the Inter99 and Health2006 studies. Filaggrin genotype was used as instrumental variable for vitamin D status. Baseline measurements of serum 25-hydroxyvitamin D were performed in all three studies. Results Instrumental variable analyses showed a 23.8% (95% confidence interval, CI 3.0, 48.6) higher HDL cholesterol level and a 30.5% (95% CI: 0.8, 51.3) lower serum level of triglycerides per doubling of vitamin D. These associations were, however, not statistically significant when applying the Bonferroni adjusted significance level. The remaining lipids showed non-significant changes in a favorable direction. Doubling of vitamin D gave a non-significantly lower odds ratio = 0.26 (95% CI: 0.06, 1.17) of the metabolic syndrome. There were no statistically significant causal effects of vitamin D status on blood pressure, body mass index, or waist circumference. Conclusion Our results support a causal effect of higher vitamin D status on a more favorable lipid profile, although more studies in other populations are needed to confirm our results.

Quantifying cardiovascular disease risk factors in patients with psoriasis: a meta‐analysis

In a previous meta‐analysis on categorical data we found an association between psoriasis and cardiovascular disease and associated risk factors.

The association of serum 25-OH vitamin D with atopy, asthma, and lung function in a prospective study of Danish adults

Besides the important skeletal functions, it has been suggested that vitamin D is involved in the pathogenesis of allergy and asthma and related to lung function. However, previous studies are inconclusive.