Abstract
Whether levels of circulating fatty acids (FAs) are associated with psoriasis and psoriatic arthritis (PsA) remains unknown. To examine the measured and predicted levels of circulating FAs in association with incident psoriatic disease, two-sample Mendelian randomisation (MR) analysis was performed to examine the causal relationship between mono- and polyunsaturated FAs (MUFAs and 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. MR analysis identified a positive association of genetically predicted MUFAs% but inverse associations of PUFAs% and PUFAs/MUFAs with psoriasis and PSA. In the cohort, higher MUFAs% was associated with increased risks of psoriasis (relative risk [RR]=1.109, P=0.004) and PsA (RR=1.188, P=0.016), while higher PUFAs% and PUFAs/MUFAs were associated with lower risks of psoriasis (RR=0.891, P=0.001) and PsA (RR=0.874, P=0.051). 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-weight participants. In conclusion, circulating PUFAs% and MUFAs% are causal factors for incident psoriatic diseases, and the effects might be modified by obesity.