Bidirectional Mendelian randomization analysis of shared genetic signals between coexisting neurodegenerative disorders to decipher underlying causal pathways

Abstract

OBJECTIVETo investigate whether coexistence of various neurodegenerative disorders is coincidental or biologically connected.\n\nDESIGNTwo sample Mendelian randomization using summary effect estimates\n\nSETTINGGenetic data taken on various neurodegenerative disorders from various cohorts comprising individuals predominantly of European ancestry.\n\nPARTICIPANTSInternational Genomics of Alzheimers patients (IGAP), project MinE, International Age-related Macular Degeneration Consortium (IAMDGC), International Multiple Sclerosis Genetics Consortium (IMSGC), International Parkinsons Disease Genomics Consortium (IPDGC)\n\nMAIN OUTCOME MEASURESAlzheimers disease (AD), Amyotrophic lateral sclerosis (ALS), Age related macular degeneration (AMD), Multiple sclerosis (MS) and Parkinsons disease (PD).\n\nRESULTSA Bonferroni corrected threshold of P=0.005 was considered to be significant, and P<0.05 was considered suggestive of evidence for a potential association. I observed a risky effect of PD on ALS (OR = 1.126, 95% CI = 1.059-1.198, P = 0.005). Using AD as exposure and PD as outcome, I observed a risky effect of AD on PD using all the MR methods with strongest results using MBE method (OR = 2.072, 95% CI = 1.006-4.028, P = 0.0416). Genetic predisposition to AD was further observed to be a risky for AMD (OR = 1.759, 95% CI = 1.040-1.974, P = 0.0363). On the contrary, AMD was observed to be strongly protective towards MS (OR = 0.861, 95% CI = 0.776-0.955, P = 0.0059).\n\nCONCLUSIONSMy findings are consistent with the previously observed relative occurrence of co-existing neurodegenerative diseases or overlapping symptoms among neurodegenerative diseases.