Causal Effect Between Natural Hair Color and Endometriosis in a European Population: A Two-Sample Mendelian Randomization

Abstract Previous observational studies have suggested an association between natural hair color and the risk of endometriosis; however, the causal relationship remains unclear. Here, we conducted a two-sample Mendelian randomization (MR) study to evaluate the potential causal link between natural hair color and endometriosis using 428 single nucleotide polymorphisms (SNPs) as genetic instruments derived from a genomewide meta-analysis comprising over 4511 cases and 227,260 controls of European ancestry. Our findings indicate that dark brown hair is associated with a decreased risk of developing endometriosis (dark brown IVW OR : 0.844, 95% CI [0.725, 0.984], p < .05). Conversely, dark hair color and lighter hair colors (red, blonde, and light brown) did not demonstrate a significant association with endometriosis risk (dark IVW OR : 0.568, 95% CI [0.280, 1.15], p = .117; red IVW OR : 1.058, 95% CI [0.719, 1.558], p = .77; blonde IVW OR: 1.158, 95% CI [0.886, 1.514], p = .28; light brown IVW OR : 1.306, 95% CI [0.978, 1.743], p = .07). These results provide compelling MR evidence supporting a causal association between natural hair color and endometriosis risk. Our findings underscore the need for larger scale studies and randomized controlled trials to delineate the biological mechanisms driving the association between hair color and endometriosis.