Parkinson’s GWAS improves when subclassifying patients by pathology, instead of clinical traits

Simón-Sánchez and Gasser discuss this in a stimulating article in the most recent issue of Neurology:

Beecham et al [2015] argue that one of the reasons for this “missing heritability” may be the uncontrolled degree of heterogeneity of [Parkinson’s Disease (PD)] in studies relying on clinical diagnosis alone. To reduce heterogeneity, they performed a GWAS in which only PD cases with autopsy-confirmed Lewy body (LB) pathology, and controls with exclusion of PD neuropathology, were included. Despite the relatively small number of samples used, they found evidence suggesting that common variation in a small region of chromosome 1p32 is associated with LB PD with a p-value just below genome-wide significance level and an odds ratio of 0.64 for the protective allele, which is comparable with that found for SNCA and MAPT in other studies. This association peak lies within PARK10, which was originally identified in a set of Icelandic families.

This “splitting” approach is likely to be valuable in other neurodegenerative diseases, as well.