A bidirectional Mendelian randomization study negates causal effects of Parkinson, Alzheimer on Basal Cell Carcinoma

Abstract

Basal cell carcinoma is the most common malignant disease of the skin. The relationship between basal cell carcinoma and neurodegenerative diseases including Parkinson’s disease and Alzheimer’s disease has been inconsistent. To determine the causal relationship, a bidirectional two sample mendelian randomization method was used to investigate causal effects. Single-nucleotide polymorphisms (SNPs) at genome-wide significance (P < 5 × 10 − 8) were identified from genome-wide association studies and a European basal cell carcinoma genome-wide association studies (GWAS) including 17,416 cases and 375,455 controls was selected. Inverse-variance weighted (IVW) method was used as the main analyses, with sensitivity analyses using weighted median and MR-PRESSO. As a result, no significance was found in the association between PKD and BCC (IVW, OR = 1.02, 95%CI[0.98–1.06], P = 0.38), neither was in AD and BCC(IVW, OR = 1.01, 95%CI[0.97–1.05], P = 0.77). Reversal estimation found no causal association between BCC and PKD(IVW-MRE, OR = 0.98, 95%CI[0.92–1.04], P = 0.45) or AD(IVW, OR = 0.98, 95%CI[0.95-1.00], P = 0.10). The results remain consistent after outlier correction and sensitivity analyses. In conclusion, PKD and AD do not necessarily reduce the risk of BCC, neither does BCC necessarily reduce the risk of PKD and AD.