Genetic heterogeneity in Parkinson disease

Abstract

Parkinson disease (PD) is considered a sporadic neurodegenerative disorder, though genetic factors are frequently involved in its etiology. That some familial presentations of PD have been associated with different mutated genes suggests that some genetic variants can also modulate the risk for “nonfamilial” presentation of PD. The hypothesis-free genome-wide association studies (GWAS) performed in PD and healthy controls1,2 revealed that certain allele variants can increase the risk of sporadic PD. Replication studies are important, since they allow investigation of whether the risk loci found in the GWAS are also associated with PD in other populations, thus excluding spurious associations that could be a result, for instance, of an undetected population structure or from genotyping errors. In this issue of Neurology ®, Sharma and colleagues3 report a replication study analyzing large PD and control samples in which they found associations of single nucleotide polymorphisms (SNPs) in 9 of the loci previously associated with PD. However, for 5 of the 9 replicated loci there was nominally significant between-site heterogeneity in the effect sizes. …