Causal association between JAK2 and erectile dysfunction: a Mendelian randomization study

Abstract

Background As one of the most critical proteins in the JAK/STAT signaling pathway, Janus kinase 2 (JAK2) is involved in many biological processes and diseases. Several observational studies have reported the role of JAK2 in erectile dysfunction. However, the causal relationship between JAK2 and erectile dysfunction remains unclear. Here we investigated the causal relationship between JAK2 and erectile dysfunction. Results Genetically predicted JAK2 was causally associated with erectile dysfunction in inverse variance weighting (OR = 1.109, 95% CI = 1.029–1.196, p = 0.007) and weighted median method (OR = 1.117, 95% CI = 1.003-1.245, p = 0.044). No heterogeneity was observed in Cochran Q-test (p = 0.855) and MR-PRESSO (p = 0.866). Pleiotropy was not observed in our study (p = 0.617). Conclusions These findings highlighted JAK2 as a risk factor for erectile dysfunction and proved the causal relationship between JAK2 and erectile dysfunction, suggesting that targeting JAK2 signaling might be a novel and promising therapeutic candidate in the treatment of erectile dysfunction.

Potential causal association between aspirin use and erectile dysfunction in European population: a Mendelian randomization study

“…Subsequently, to mitigate biased outcomes induced by linkage disequilibrium (LD), a clumping process was carried out with an r 2 = 0.001 cutoff and a window size of 10,000 kb. The Phenoscanner database (version 2.0) ( http://www.phenoscanner.medschl.cam.ac.uk/ ) was then utilized to sieve genetic variants associated with confounding factors, including diabetes, obesity, education, sleeplessness or insomnia, psychiatric factors such as anxiety, depression, and bipolar disorder, and removing SNPs associated with any of these potential confounders on a genome-wide basis ( 20 – 24 ). If the previously screened SNPs were not present in the outcome GWAS data, proxy SNPs (high LD of r 2 >0.8 with the target SNPs) would be sought as replacements.…”