An international team of researchers conducting a genome-wide association study (GWAS) has discovered that common variants in immune system genes are linked to Parkinson’s disease.
The study was the work of the NeuroGenetics Research Consortium, led by Dr Haydeh Payami, a research scientist at the Health Wadsworth Center and professor in the School of Public Health, both in the New York State Department of Health. The Consortium wrote a paper on the study that was published online in Nature Genetics on 15 August.
One of the Consortium clinical directors, Dr Cyrus Zabetian, associate professor of neurology at the University of Washington and VA Puget Sound Health Care System, Stewart Factor at Emory University, told the media that for some years now scientists have seen “subtle hints” that immune function and Parkinson’s disease might be linked:
“But now we have much more convincing evidence of this and a better idea of which parts of the immune system might be involved,” he added.
For the study, the researchers examined over 2,000 volunteer patients with Parkinson’s and nearly 2,000 healthy volunteers from clinics in Oregon, Washington, New York and Georgia.
Payami thanked the volunteers for their help, many of whom had been with the study for nearly 20 years:
“This type of research could not be done if it weren’t for the willing and dedicated individuals who volunteer as research subjects,” she said.
Payami and colleagues scanned the genomes of all 4,000 volunteers. They also assessed a number of clinical and environmental factors that might contribute to the development and progress of Parkinson’s disease and its complications.
They wrote that they replicated already published links with three genes: SNCA, MAPT, and GAK, and detected new links with common variants in the HLA region that was “uniform across all genetic and environmental risk strata and was strong in sporadic … and late-onset [Parkinson’s] disease”.
The HLA (human leukocyte antigen) region of the human genome is home to a large number of immune system genes that are important for recognizing foreign agents and differentiating them from the body’s own tissue. HLA molecules also help ensure that the immune system does not attack the body’s own tissue.
However, this part of the immune system does not always work as well as it should: certain HLA variants are linked to increased risk of disease, or higher protection against them, while other variants can trigger autoimmune disorders where the immune system can’t distinguish between the body’s own tissue and foreign agents and attacks both with equal force.
For example, the neurological autoimmune disease multiple sclerosis, is linked to the gene HLA-DR.
Based on this finding, Payami and colleagues said they plan to take a fresh look at the possible role of infection, inflammation and autoimmunity in Parkinson’s disease.
Their work could help find better drugs for treating Parkinson’s. For example, we already know that some people who take non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, have a reduced risk of developing Parkinson’s, but this effect is not the same in everyone and NSAIDs can also have side effects. A closer investigation of the relevant gene variants could help develop more selective treatments for Parkinson’s.
The team will also be investigating some other genes they came across in their GWAS but they now need to confirm a link with Parkinson’s.
They will also be “mining” the huge piles of data from the study to look for evidence of gene-environment interactions, for instance there may be triggers in the environment that switch certain genes related to Parkinson’s on and off; such discoveries also help in the search for more personalized treatments.
Financial backing for the study came from the National Institute of Neurological Disorders and Stroke and a Edmond J. Safra Global Genetic Consortium grant from the Michael J. Fox Foundation for Parkinson’s Disease Research.
“Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease.”
Taye H Hamza, Cyrus P Zabetian, Albert Tenesa, Alain Laederach, Jennifer Montimurro, Dora Yearout, Denise M Kay, Kimberly F Doheny, Justin Paschall, Elizabeth Pugh, Victoria I Kusel, Randall Collura, John Roberts, Alida Griffith, Ali Samii, William K Scott, John Nutt, Stewart A Factor & Haydeh Payami.
DOI:10.1038/ng.642
Additional source: University of Washington.
Written by: Catharine Paddock, PhD