Multiple candidate gene analysis identifies α-synuclein as a susceptibility gene for sporadic Parkinson's disease

摘要

Parkinson's disease (PD), one of the most common human neurodegenerative diseases, is characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain. PD is a complex disorder with multiple genetic and environmental factors influencing disease risk. To identify susceptible genes for sporadic PD, we performed case–control association studies of 268 single nucleotide polymorphisms (SNPs) in 121 candidate genes. In two independent case–control populations, we found that a SNP in α-synuclein (SNCA), rs7684318, showed the strongest association with PD (P=5.0×10−10). Linkage disequilibrium (LD) analysis using 29 SNPs in a region around rs7684318 revealed that the entire SNCA gene lies within a single LD block (D′>0.9) spanning ∼120 kb. A tight LD group (r2