Genetic associations between polyunsaturated fatty acids and alopecia areata

The influence of circulating polyunsaturated fatty acids (PUFAs) on alopecia areata (AA) development remains poorly understood, with inconsistent results reported. Our study aims to evaluate their causal associations using the bidirectional Mendelian randomization method. European ancestry genome-wide association studies were used to analyze the genetic associations between PUFAs and AA (n = 211,428). Sample sizes for PUFAs were 13,527, 13,506, 114,999, 7818, and 13,549 for plasma linoleic acid (LA), omega-6, omega-3, docosahexaenoic acid (DHA), and PUFAs other than 18:2 (otPUFA), respectively. The causal associations were primarily determined by the inverse variance weighted (IVW) method. Circulating omega-6 (IVW odds ratio [OR] = 1.64, 95% confidence interval [CI] = 1.15-2.33, P = .0059) and LA (IVW OR = 1.49, 95% CI = 1.05-2.13, P = .0257) were positively associated with AA risk. Conversely, AA was negatively correlated with circulating DHA (IVW OR = 0.99, 95% CI = 0.99-1.00, P = .0324). Elevated circulating omega-6 and LA are correlated with an increased AA risk. Furthermore, AA was negatively associated with circulating DHA. These findings provide insights into the potential biological mechanisms underlying the development of AA, offering potential implications for dietary recommendations and treatment options.