Parkinson disease (PD) is a common disorder that leads to motor and cognitive disability. We performed a genome-wide association study (GWAS) with 2000 PD and 1986 control Caucasian subjects from NeuroGenetics Research Consortium.1–5 We confirmed SNCA2,6–8 and MAPT3,7–9; replicated GAK9 (PPankratz+NGRC=3.2×10−9); and detected a novel association with HLA (PNGRC=2.9×10−8) which replicated in two datasets (PMeta-analysis=1.9×10−10). We designate the new PD genes PARK17 (GAK) and PARK18 (HLA). PD-HLA association was uniform across genetic and environmental risk strata, and strong in sporadic (P=5.5×10−10) and late-onset (P=2.4×10−8) PD. The association peak was at rs3129882, a non-coding variant in HLA-DRA. Two studies suggested rs3129882 influences expression of HLA-DR and HLA-DQ.10,11 PD brains exhibit up-regulation of DR antigens and presence of DR-positive reactive microglia.12 Moreover, non-steroidal anti-inflammatory drugs (NSAID) reduce PD risk.4,13 The genetic association with HLA coalesces the evidence for involvement of the immune system and offers new targets for drug development and pharmacogenetics.

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Using oligonucleotide primers designed to match conserved regions of mammalian mitochondrial DNA (mtDNA), we have amplified and sequenced two divergent cytochrome b nuclear pseudogenes from orangutan cellular DNA. Evolutionary analysis suggests that a nuclear transfer occurred about 30 million years ago on the lineage leading to the catarrhines (Old World monkeys and hominoids), and involved a long (at least 3 kilobases), probably damaged, piece of mtDNA. After this transfer, the pseudogene duplicated, giving rise to the two copies that are probably present in all hominoids, including humans. More recent transfers involving the entire cytochrome b gene have also occurred in the Old World monkeys. Such nuclear copies of mtDNA can confound phylogenetic and population genetic studies, and be an insidious source of DNA contamination of 'ancient' and forensic DNA. Indeed, contamination with these anciently transferred human pseudogenes is almost certainly the source of the cytochrome b sequences recently reported from 'dinosaur bone DNA'.