Reply to Liu et al.: Tissue specificity of SIM1 gene expression and erectile dysfunction

In our study (1), we identify a locus in the human genome near the SIM1 gene that is significantly associated with the risk of erectile dysfunction. Through differential enhancer assays, we demonstrate that the lead single-nucleotide polymorphism (SNP), rs17185536, alters enhancer activity. Furthermore, long-range chromatin interaction experiments show that the region containing the lead variant likely interacts with the promoter of the SIM1 gene. Based on the evidence from these analyses, we hypothesize that a regulatory element harboring rs17185536 or other erectile dysfunction-associated SNPs in the locus affects SIM1 expression. Previous research found that male mice lacking the melanocortin 4 receptor ( Mc4r ) showed … [↵][1]1To whom correspondence may be addressed. Email: eric.jorgenson{at}kp.org or stephen.vandeneeden{at}kp.org. [1]: #xref-corresp-1-1