The Causal Effect of Iron Traits on Risk of Hypertrophic Scarring: A Two‐Sample Mendelian Randomization Study

Summary

This two-sample Mendelian randomization study investigated causal relationships between iron metabolism traits and hypertrophic scarring risk using genome-wide association study data from multiple consortia and the FinnGen cohort. The analyses found no significant causal associations between iron deficiency anaemia, transferrin, ferritin, or iron levels and hypertrophic scarring; however, the inverse-variance weighted method suggested a potential protective effect of elevated transferrin saturation (OR = 0.69, 95% CI 0.51–0.93). The authors conclude that whilst further investigation of iron metabolism's role in wound healing and fibrotic processes is warranted, the evidence does not presently support strong causal links between most iron traits and scarring.

Regional applicability

This is a genetic association study using international GWAS data and the Finnish FinnGen cohort; findings are applicable to populations of European ancestry and would be broadly relevant to United Kingdom clinical practice, though direct wound healing intervention trials in UK populations would be needed to establish clinical utility.

Key measures

Odds ratios (OR) for causal associations between iron traits and hypertrophic scarring; transferrin saturation OR = 0.69 (95% CI 0.51–0.93); pleiotropy and heterogeneity assessed via MR-Egger intercept, Cochran's Q test, and MR-PRESSO

Outcomes reported

The study examined whether iron deficiency anaemia, transferrin, transferrin saturation, ferritin, and iron levels have causal associations with hypertrophic scarring risk using two-sample Mendelian randomization. Results indicated no significant causal links for most iron traits, though elevated transferrin saturation showed a potential protective effect on scarring risk.

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