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

Yuping Zhang, Ying Feng
Twin research and human genetics : the official journal of the International Society for Twin Studies · 2025 · vol. 28(1) , pp. 42–52 · doi:10.1017/thg.2025.1 · PMID:39995152 · W4407929148
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This Mendelian randomization study found that dark brown hair color is associated with a decreased risk of endometriosis in European populations, while other hair colors showed no significant association.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 ⓘ

This study used a two-sample Mendelian randomization design to test whether genetically influenced natural hair color (blonde, red, light brown, dark brown, and black) causally affects endometriosis risk in a European population, using 428 UK Biobank-derived SNPs as instrumental variables for hair color and UK Biobank summary data for female European ancestry endometriosis (4511 cases, 227,260 controls). The primary analysis applied inverse-variance weighting with multiplicative random effects, with additional Mendelian randomization methods (MR Egger, weighted median/mode, and BWMR) planned to address pleiotropy and robustness, and the paper notes key IV assumptions as limitations (no unmeasured confounding and effects only through exposure). A specific caveat is that the hair color exposure was captured from a questionnaire about “natural hair color” (with pre-greying considered), and the truncated text indicates only the start of sensitivity analyses beyond this. This paper is centrally about endometriosis — it uses causal inference (two-sample MR) to evaluate whether natural hair color is causally related to endometriosis risk.

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Abstract

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.

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Condition tags

endometriosis

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References (53)

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