Genome-Wide Association Study reveals genetic risk underlying Parkinson’s disease

By J. Simón-Sánchez, Claudia Schulte, J. Bras, Manu Sharma, Raphael J. Gibbs, Daniela Berg, C. Paisán-Ruiz, Peter Lichtner, S. Scholz, Dena G. Hernandez and 36 more. Nature Genetics, 2009

1,913 citations recorded by the source corpus.

We performed a genome-wide association study (GWAS) in 1,713 individuals of European ancestry with Parkinson's disease (PD) and 3,978 controls. After replication in 3,361 cases and 4,573 controls, we observed two strong association signals, one in the gene encoding α-synuclein (SNCA; rs2736990, OR = 1.23, P = 2.24 × 10−16) and another at the MAPT locus (rs393152, OR = 0.77, P = 1.95 × 10−16). We exchanged data with colleagues performing a GWAS in Japanese PD cases. Association to PD at SNCA was replicated in the Japanese GWAS, confirming this as a major risk locus across populations. We replicated the effect of a new locus detected in the Japanese cohort (PARK16, rs823128, OR = 0.66, P = 7.29 × 10−8) and provide supporting evidence that common variation around LRRK2 modulates risk for PD (rs1491923, OR = 1.14, P = 1.55 × 10−5). These data demonstrate an unequivocal role for common genetic variants in the etiology of typical PD and suggest population-specific genetic heterogeneity in this disease.

Subfields: Cognitive Neuroscience, Neurology

View Paper: https://www.semanticscholar.org/paper/0e388a0d20dca554637bca62549b7177f0d9ff35

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In Cognitive Neuroscience

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Citations in the corpus

The genetics of Alzheimer disease: back to the future. (2010, positive): “15 for all three loci), which is much less than for APOE 34 (allelic OR 4) or other established neurodegenerative disease loci (e.g., ORs > 1.3 for three of the established Parkinson susceptibility loci—SNCA, MAPT, and LRRK2—which were all confirmed by different GWAS; Pankratz et al., 2009; Simón-Sá”
Clinical Neurology and Epidemiology of the Major Neurodegenerative Diseases. (2018, positive): “Single nucleotide polymorphisms (SNPs) in SNCA were reported to be associated with PD and MSA (Scholz et al. 2009; Simon-Sanchez et al. 2009), and mutations in COQ2 were found in familial MSA cases in Japan (Multiple-System Atrophy Research Collaboration 2013).”
Pathological α-Synuclein Transmission Initiates Parkinson-like Neurodegeneration in Nontransgenic Mice (2012, neutral): “The etiology of these processes remains unclear, although in familial PD, autosomal dominant α-Syn gene mutations or amplifications directly link α-Syn dysfunction to disease causation (2, 3).”
Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease (2010, neutral): “(7) No blood-relation to other subjects.”
Missing pieces in the Parkinson's disease puzzle (2010, neutral): “Recently, genome-wide association studies (GWASs) have provided evidence for a contribution of common genetic variability in α-synuclein and microtubule-associated protein tau (MAPT) to Parkinson's diseas”
Epidemiology and etiology of Parkinson’s disease: a review of the evidence (2011, neutral): “mentioned above [262, 263] as well as a replication study of a Chinese sample [264] reported”
Neuroinflammation in Parkinson’s disease and its potential as therapeutic target (2015, positive): “In the last several years, the common variations in leucine-rich repeat kinase 2 (LRRK2) gene have been identified as risk factors of both familial and sporadic PD [67–70].”