ABSTRACT
OBJECTIVE To investigate whether coexistence of various neurodegenerative disorders is coincidental or biologically connected.
DESIGN Two sample Mendelian randomization using summary effect estimates
SETTING Genetic data taken on various neurodegenerative disorders from various cohorts comprising individuals predominantly of European ancestry.
PARTICIPANTS International Genomics of Alzheimer’s patients (IGAP), project MinE, International Age-related Macular Degeneration Consortium (IAMDGC), International Multiple Sclerosis Genetics Consortium (IMSGC), International Parkinson’s Disease Genomics Consortium (IPDGC)
MAIN OUTCOME MEASURES Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), Age related macular degeneration (AMD), Multiple sclerosis (MS) and Parkinson’s disease (PD).
RESULTS A 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).
CONCLUSIONS My findings are consistent with the previously observed relative occurrence of co-existing neurodegenerative diseases or overlapping symptoms among neurodegenerative diseases.