Psoriasis and Alzheimer disease:a two-sample two-way Mendelian randomization study
Objective To analyze whether there is a causal association between psoriasis and Alzheimer disease(AD)by a two-sample two-way Mendelian randomization(MR)method.Methods In the forward study,the single nucleotide polymorphisms(SNPs)associated with psoriasis were obtained from the comprehensive statistical data of the genome-wide association study database as the instrumental variables,and AD as the outcome;in the reverse study,the SNPs associated with AD were taken as instrumental variables,and psoriasis as the outcome.Using two-sample two-way MR analysis,the odds ratio(OR)value and 95％confidence interval(CI)of regression models,namely inverse variance weighted(IVW)method,MR-Egger regression method,weighted median method,simple pattern method,and weighted pattern method,were used to evaluate the causal relationship between psoriasis and AD.Cochran's Q test was used to assess the heterogeneity of genetic instrumental variables,MR-Egger intercept method was used to test the horizontal pleiotropy of the assessment,"leave-one-out"method was used to assess the sensitivity of a SNP to the effect of causality,and the symmetry of funnel plot was observed to assess bias.Results A total of 19 SNPs associated with psoriasis were included as instrumental variables in the forward study.The IVW analysis of the forward study showed that there was a causal correlation between psoriasis and AD[OR=1.032,95％CI(1.014,1.051),P＜0.001],and MR-Egger regression method[OR=1.042,95％CI(1.012,1.073),P=0.013],weighted median[OR=1.048,95％CI(1.023,1.074),P＜0.001],and weighted model[OR=1.046,95％CI(1.020,1.073),P=0.002]all supported this result.Heterogeneity test(IVW result:Q=13.752,P=0.745;MR-Egger regression result:Q=13.134,P=0.727),MR-Egger intercept method(Egger intercept=-0.004,P=0.442),the results of"leave-one-out"method and funnel plot showed that the results of MR analysis were reliable.A total of 127 AD-related SNPs were included as instrumental variables in the reverse study.In reverse research,there was no evidence to support the AD could increase the risk of psoriasis(P＞0.05).Heterogeneity test(IVW result:Q=232.496,P＜0.001;MR-Egger regression result:Q=232.119,P＜0.001)suggested heterogeneity,but MR-Egger intercept method(Egger intercept=0.003,P=0.652),the results of"leave-one-out"method and funnel plot showed that the results of MR analysis were reliable.Conclusion There is a causal association between psoriasis and AD,and psoriasis may increase the risk of AD.
PsoriasisAlzheimer diseaseMendelian randomizationcausal association
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NSTL
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