Scientists have identified new genetic factors that contribute to the risk of developing Parkinson’s disease

Researchers have discovered new genetic factors that contribute to the risk of developing Parkinson’s disease, according to a Northwestern Medicine study published in the journal Brain.

The results show novel short DNA tandem repeat sequences in four distinct regions, independent of currently known Parkinson’s disease risk variants, that could serve as novel therapeutic targets.

Short tandem repeat sequences consist of units of two to thirteen nucleotides repeated hundreds of times in a single DNA strand.

“We are showing for the first time that these complex repetitive regions actually influence an individual’s disease risk, underestimating the understanding of all the complex genetic factors,” said the doctor behind this devastating disease.

Parkinson’s disease is strongly influenced by genetic factors, and more than 90 types of genetic variants are known to increase the risk of developing Parkinson’s disease.

However, these variants account for less than half of all known genetic factors influencing disease risk, highlighting the need for further research.

In particular, short tandem repeats—short DNA sequences that repeat several times next to each other—are thought to contribute to the heritability of Parkinson’s disease, but remain unexplored due to the lack of effective methods of analysis.

To determine whether short tandem repeats actually play a role in increasing the risk of Parkinson’s disease, the researchers conducted a meta-analysis (statistical analysis) of genomic data collected from 40,000 people registered with the International Parkinson’s Genetic Consortium in collaboration with the Laboratory. of Neurogenetics National Institutes of Health.

This detailed analysis identified 34 new genetic variants, 88 percent of which are closely related variants previously known to increase the risk of Parkinson’s disease.

However, the researchers found new short tandem repeats around four genes not known to contribute to the risk of Parkinson’s disease: NDUFAF2, TRIML2, MIRNA-129-1 and NCOR1.

In addition, these short tandem repeats also affected the expression of nearby genes, which the researchers say could provide more information about how these variants increase the risk of Parkinson’s disease.

“These independent short tandem repeats will be used as candidates for further functional follow-up research to learn more about the functional implications of these variants and their impact on these genes in Parkinson’s disease,” said Bernabe Ignacio Bustos, postdoctoral fellow. in Loeb’s lab and lead author of the study.

Loeb noted that further research is needed on these new short tandem repeats to elucidate their exact role in the genome in the context of Parkinson’s disease, which could help develop new treatment strategies.

He explained: “Incorporating these findings into existing risk prediction models is important to identify the people most at risk of developing Parkinson’s disease. Unfortunately, at the cellular level, we do not yet know how these frequencies lead to Parkinson’s disease, but they are candidates for further research that we hope will bring us one step closer to identifying a new therapeutic target.”

Source: Medical Express