Importance: Psoriasis, psoriatic arthritis, and inflammatory bowel disease, ie, Crohn disease and ulcerative colitis, are chronic systemic immune-mediated disorders affecting an increasing proportion of adults and children worldwide. Observational studies have suggested an association between inflammatory bowel disease and psoriasis and vice versa. So far, however, it remains unclear whether and in which direction causal relationships exist.Objective: To investigate the association between inflammatory bowel disease, particularly Crohn disease and ulcerative colitis, and psoriasis or psoriatic arthritis.Design, Setting, and Participants: A bidirectional 2-sample mendelian randomization study was conducted using summary statistics from genome-wide association studies including up to 463 372 European individuals. Total and direct effects were derived performing an iterative radial and robust inverse-variance weighted method within the univariable and multivariable mendelian randomization setting, respectively. Causal estimates were verified using a validation inflammatory bowel disease sample, a series of pleiotropy-robust mendelian randomization methods, and sensitivity analyses based on a PhenoScanner search in conjunction with network analysis. Data analysis was performed from April to May 2022.Main Outcomes and Measures: Inflammatory bowel disease, Crohn disease, ulcerative colitis, psoriasis, and psoriatic arthritis were used as both exposures and outcomes.Results: The European samples included 12 882 cases of inflammatory bowel disease and 5621 cases of psoriasis. The proportion of women ranged between 48% and 56%. Genetically predicted inflammatory bowel disease was associated with higher risk of psoriasis (pooled odds ratio [OR], 1.10; 95% CI, 1.05-1.15; P < .001) and psoriatic arthritis (pooled OR, 1.10; 95% CI, 1.04-1.18; P = .003). In contrast with ulcerative colitis, the Crohn disease subentity was associated with psoriasis (OR, 1.16; 95% CI, 1.12-1.20; P < .001) and psoriatic arthritis (OR, 1.13; 95% CI, 1.06-1.20; P < .001). Regarding the reverse directions, no notable associations could be found.Conclusions and Relevance: Findings of this mendelian randomization study support a causal effect between inflammatory bowel disease and psoriasis as well as psoriatic arthritis, but not vice versa. It seems that especially Crohn disease and not ulcerative colitis is responsible for the causal effect of inflammatory bowel disease on both psoriasis outcomes. These findings have implications for the management of inflammatory bowel disease and psoriasis in clinical practice.

Recent studies suggested obesity to be a possible risk factor for COVID-19 disease in the wake of the coronavirus (SARS-CoV-2) infection. However, the causality and especially the role of body fat distribution in this context is still unclear. Thus, using a univariable as well as multivariable two-sample Mendelian randomization (MR) approach, we investigated for the first time the causal impact of body composition on the susceptibility and severity of COVID-19. As indicators of overall and abdominal obesity we considered the measures body mass index (BMI), waist circumference (WC), and trunk fat ratio (TFR). Summary statistics of genome-wide association studies (GWASs) for these body composition measures were drawn from the GIANT consortium and UK Biobank, while for susceptibility and severity due to COVID-19 disease data from the COVID-19 Host Genetics Initiative was used. For the COVID-19 cohort neither age nor gender was available. Total and direct causal effect estimates were calculated using Single Nucleotide Polymorphisms (SNPs), sensitivity analyses were done applying several robust MR techniques and mediation effects of type 2 diabetes (T2D) and cardiovascular diseases (CVD) were investigated within multivariable MR analyses. Genetically predicted BMI was strongly associated with both, susceptibility (OR = 1.31 per 1 SD increase; 95% CI: 1.15–1.50; P-value = 7.3·10−5) and hospitalization (OR = 1.62 per 1 SD increase; 95% CI: 1.33–1.99; P-value = 2.8·10−6) even after adjustment for genetically predicted visceral obesity traits. These associations were neither mediated substantially by T2D nor by CVD. Finally, total but not direct effects of visceral body fat on outcomes could be detected. This study provides strong evidence for a causal impact of overall obesity on the susceptibility and severity of COVID-19 disease. The impact of abdominal obesity was weaker and disappeared after adjustment for BMI. Therefore, obese people should be regarded as a high-risk group. Future research is necessary to investigate the underlying mechanisms linking obesity with COVID-19.

Background: The question of whether asthma is causally related to gastrointestinal disorders remained unanswered so far. Thus, this study investigated whether there is such a relation and whether the time of onset of asthma plays a role in the occurrence of the following gastrointestinal disorders: peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD) including the distinction between Crohn’s disease (CD) and ulcerative colitis (UC).Methods: Using summary data of genome-wide association studies (GWASs), we ran Mendelian randomization analyses based on up to 456,327 European participants. Outlier assessment, a series of sensitivity analyses and validation of IBD results in a second GWAS were performed to confirm the results.Results: Presented ORs represent the average change in the outcome per 2.72-fold increase in the prevalence of the exposure. Genetically predicted childhood-onset asthma was positively associated with PUD, GORD, and IBS with similar odds ratios near 1.003 and adjustedP-values from 0.007 (GORD) to 0.047 (PUD). Furthermore, it was inversely related to IBD (OR = 0.992, 95% CI: 0.986, 0.998, adjustedP = 0.023) and suggestively associated with its UC subtype (OR = 0.990, 95% CI: 0.982, 0.998, adjustedP = 0.059). There were no associations between genetically predicted adult-onset asthma and the mentioned gastrointestinal disorders.Conclusions: This study provides evidence that the presence of asthma onset in childhood increases the risk for GORD, PUD, and IBS but decreases the risk for IBD in adults. The lower risk for IBD may be attributed to a lower risk primarily for UC.

A number of prior studies have examined the association between anthropometric measures and mortality, but studies investigating the sex-specific predictive value of novel anthropometric measures on mortality are scarce so far. Therefore, we investigated the sex-specific relevance of the new anthropometric measures body adiposity index (BAI) and waist to height ratio (WHtR) as well as the common measures body mass index (BMI), waist circumference (WC), and waist to hip ratio (WHR) for cause-specific mortality risk. The analysis was based on data from the German population based KORA (Cooperative Health Research in the Region of Augsburg) Augsburg cohort study. A total of 6670 men and 6637 women aged 25 to 74 years at baseline examination were included. During a mean follow-up period of 15.4 years, 2409 persons died. Via Cox proportional hazard regression, the associations between the different anthropometric measures and all cause-, cardiovascular disease (CVD)- and cancer mortality were assessed. BMI, WC, and WHR were significantly associated with all-cause and CVD-mortality in both sexes. WC and WHR were particularly associated with higher all-cause and CVD-mortality risk in women, while in men especially WHtR and BAI were strongly related to these outcomes. Females with WC, WHtR, and WHR measures in the 4th quartile compared with women in the 2nd quartile had a higher risk of death from cancer. Contrary, men in the lowest quartile of WC and WHtR in comparison to men in the 2nd quartile had a significantly elevated cancer mortality risk. BAI was no risk predictor for all-cause and cause-specific mortality in women. Central obesity reflects higher all-cause and CVD-mortality risk particularly in women. BAI and WHtR seem to be valid as risk predictors for all-cause and especially CVD mortality in men but not women. There are marked sex-differences regarding cancer mortality risk for the different anthropometric measures.

Emerging evidence from observational studies suggests an increased risk of Parkinson’s disease (PD) in patients with inflammatory bowel disease (IBD). However, to date it is not clear whether a causal relationship exists. To investigate whether IBD is causally related to PD, a two-sample Mendelian randomization study was carried out. Independent genetic instruments from the largest available genome-wide association study (GWAS) for IBD (7045 cases, 456,327 controls) including European participants were used to investigate the association with PD (56,306 cases; 1.4 million controls). The results were validated by using a second IBD sample (12,882 cases; 21,770 controls) including the main subtypes ulcerative colitis (UC; 6968 cases; 20,464 controls) and Crohn’s disease (CD; 5956 cases; 14,927 controls). The radial inverse-variance weighted (IVW) approach was used in the primary analysis, and the robustness of the findings were confirmed in a number of sensitivity analyses. Finally, the recently proposed CAUSE approach was performed. There was no evidence of an association between IBD and PD (OR_IVW = 0.98; 95% CI: [0.93; 1.04]; P = 0.48). This finding could be validated using a second sample of IBD cases (OR_IVW = 0.98; 95% CI: [0.95; 1.02]; P = 0.36). Furthermore, MR analyses did not support a causal effect of CD (OR_IVW = 1.00; 95% CI: [0.98; 1.03]; P = 0.96) or UC (OR_IVW = 1.02; 95% CI: [0.98; 1.06]; P = 0.45) on PD. The present study suggests that neither IBD nor its subtypes CD and UC causally affect Parkinson’s disease in the European population. Further research is necessary to investigate whether intestinal inflammation impacts the development of PD.