Progressive supranuclear palsy (PSP) is a rare movement disorder caused by damage to certain areas of the brain. People with PSP experience increasing difficulty balancing and walking and suffer from frequent falls, in addition to varying vision, mood, and cognitive problems. PSP is similar to Parkinson’s disease but is much rarer — about 20,000 people in the United States are currently diagnosed with PSP.
As with Parkinson’s disease, the development of PSP is complex and influenced by many genetic and environmental factors. One genetic factor in particular, a variant in the MAPT gene, has been repeatedly linked to the disease. The MAPT gene codes for a protein called tau that is found in abnormally high amounts in the neurons of people with PSP. Scientists believe there are multiple factors interacting in this region of the genome that affect PSP development, but little is known about this interaction and how other genetic variation might contribute to PSP risk.
To discover common genetic variants potentially influencing risk for this disease, an international team of researchers led by Gunter Höglinger of Philipps-Universitat in Germany studied more than 2,000 individuals of European descent diagnosed with PSP, comparing their DNA to that of nearly 7,000 healthy European individuals. The results, published last month in the journal Nature Genetics, reported several SNPs associated with the disease.
One of the SNPs reported by Höglinger’s team is located in MAPT and is closely linked to the already well-established variant for PSP risk. In this study, each copy of the G version of this SNP was associated with about 5.5 times lower odds of the disease. The researchers suggest that much of this effect is due to the SNP’s strong correlation with the previously known MAPT variant.
In addition to the strong association at MAPT, the researchers identified three other genetic variants with smaller effects on PSP risk located in the STX6, EIF2AK3, and MOBP genes. These genes have intriguing connections to PSP and other neurodegenerative diseases but further research is needed to determine the exact roles they play in the development of these conditions.