Abundances but not concentrations of circulating unsaturated fatty acids are associated with incident psoriatic diseases: Evidence from cohort and Mendelian randomization studies

Whether the levels of circulating fatty acids (FAs) are associated with psoriasis and psoriatic arthritis remains unknown. To examine the measured and predicted levels of circulating FAs in association with incident psoriatic disease, 2-sample Mendelian randomization analysis was performed to examine the causal relationship between monounsaturated FAs (MUFAs) and polyunsaturated FAs (PUFAs) and psoriasis, and a cohort study of the UK Biobank participants was conducted to validate the findings, in terms of the measured and dietarily predicted levels of FAs. Mendelian randomization analysis identified a positive association of genetically predicted MUFAs% but inverse associations of PUFAs% and PUFAs/MUFAs with psoriasis and psoriatic arthritis. In the cohort, higher MUFAs% was associated with increased risks of psoriasis (relative risk = 1.109, <i>P</i> = .004) and psoriatic arthritis (relative risk = 1.188, <i>P</i> = .016), whereas higher PUFAs% and PUFAs/MUFAs were associated with lower risks of psoriasis (relative risk = 0.891, <i>P</i> = .001) and psoriatic arthritis (relative risk = 0.874, <i>P</i> = .051). Dietary scores that predict PUFAs% and MUFAs% showed consistent results with larger effect sizes. The effects of PUFAs% and MUFAs% were not significant in under- or normal-weighted participants. In conclusion, circulating PUFAs% and MUFAs% are causal factors for incident psoriatic diseases, and the effects might be modified by obesity.