Sporadic and rare familial forms of Parkinson’s disease are related, and common genetic variability plays a role in developing the disorder, according to collaborating scientists from the U.S. and Europe. The researchers confirmed that mutations in the alpha-synuclein (SNCA) gene and microtubule associated protein tau (MAPT), both present in the general population, are risk factors for sporadic Parkinson disease.
An independent study from Japan identified a different combination of genetic variants as risk factors in people of Japanese descent. The researchers suggest that this data demonstrates a role for common genetic variants in the etiology of typical Parkinson’s disease and implicates population-specific genetic heterogeneity in the disease.
The finding came from the largest genome-wide association study (GWAS) reported to date for Parkinson’s disease, involving 14,000 DNA samples. The research is presented in the November 15 online issue of Nature Genetics in a paper titled “Genome-wide association study reveals genetic risk underlying Parkinson's disease.”
“Because previous Parkinson's GWAS were too small and lacked power, we worked together to compile and analyze the large data sets needed to identify the elusive genetic variations that play a role in this complex disease,” says Andrew B. Singleton, Ph.D., chief of the NIA laboratory of neurogenetics, one of the study leaders.
Following the initial findings implicating SNCA and MAPT variants as risk factors for typical Parkinson’s disease, the team then compared results with researchers performing a GWAS study in a group of Japanese people. This second GWAS also revealed a strong association for SNCA but not for MAPT.
Additionally, both GWAS studies found evidence for two additional risk variants. The first, which was strongest in the Japanese population, was named Park16. The second is close to the LRRK2 gene that the contains mutations that cause an inherited form of Parkinson disease.