Genetically predicted ankylosing spondylitis is causally associated with psoriasis

Abstract

BackgroundPrevious observational studies have reported the striking association between ankylosing spondylitis (AS) and psoriasis, but the causal relationship between the two diseases remains unclear.MethodsTwo-sample Mendelian randomization (MR) analysis with methods of inverse-variance weighted, MR-Egger regression, weighted median, and weighted mode was conducted to evaluate the bidirectional causal associations between AS and psoriasis. Effective single-nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS) were selected as instrumental variables (IVs). Sensitivity analyses were also applied to verify whether heterogeneity and pleiotropy can bias the results.ResultWe found positive causal effects of genetically increased AS risk on psoriasis (IVW: OR = 1.009, 95% CI = 1.005–1.012, p = 8.07E-07). Comparable outcomes were acquired by MR-Egger regression, weighted median, and weighted mode approaches. Nevertheless, we did not find significant causal effects of psoriasis on AS (IVW: OR = 1.183, 95% CI = 0.137–10.199, p = 0.879). The sensitivity analyses showed that the horizontal pleiotropy was unlikely to skew the causality. The leave-one-out analysis demonstrated that no single SNP can drive the MR estimates. No evidence of heterogeneity was found between the selected IVs.ConclusionOur findings provide evidence that AS has positive causal effects on the risk of psoriasis in the European population.

Causal relationships between CD25 on immune cells and hip osteoarthritis

“…Nevertheless, there are some limitations in this study. Firstly, this study relies on publicly available GWAS data, which hinders the possibility of subgroup analysis considering factors like gender, age, and BMI to further explore the effects of other relevant factors on hip OA ( 26 ). Secondly, given that the dataset exclusively represents a European population, generalizing the findings to other ethnic groups should be done cautiously, necessitating further scrutiny ( 27 ).…”

“…Conversely, the execution of randomized controlled trials (RCTs) encounters an array of practical limitations that render their implementation within clinical environments a formidable undertaking (23). Mendelian randomization (MR) emerges as an analytical methodology aimed at examining potential causal links between exposures and outcomes, utilizing data derived from genome-wide association studies (GWAS) (23)(24)(25)(26)(27)(28). MR uses exposure-related genetic variations as instrumental variables (IVs) and follows the Mendelian gamete random allocation principle as well as the principle of free combination.…”

No causal effect of genetically determined circulating homocysteine levels on psoriasis in the European population: evidence from a Mendelian randomization study

“…Consequently, the challenges posed by confounding and reverse causation, commonly encountered in observational studies, can be circumvented, which enables the estimation of the causal impact of a risk factor on a particular outcome of interest (31)(32)(33). Previous research has explored the causal association between psoriasis and alcohol consumption (34), smoking (34), body mass index, vitamin D levels (35,36), serum lipids (37,38), COVID-19 (39), inflammatory bowel diseases (40), cardiovascular diseases (10,41), non-alcoholic liver diseases (42), ankylosing spondylitis (43), and lung cancer (44,45) via the MR approach. However, there is a scarcity of research investigating the causal effect of plasma Hcy levels on psoriasis.…”