Genetics and stem cells

Genetics of Parkinson's explored

"The immune system may have a key role in the development of Parkinson's disease," reported BBC News. It said that a study has found an association between genes controlling immunity and the condition Parkinson’s disease.

The news reports appear to be accurate. This well-conducted, genome-wide association study found that particular genetic variants involved in the immune system are associated with Parkinson’s disease. While on its own, this region is only associated with a modest effect on Parkinson’s disease risk, the cumulative effect of this new association and others already identified is thought to be quite substantial.

These findings may contribute to treatments or better detection of Parkinson’s, but it is too soon to realise the full implications of these findings.

Where did the story come from?

The study was carried out by researchers from the New York State Department of Health and several other academic and medical centres in the USA. The work was funded by the National Institute of Neurological Disorders and Stroke, with support from several American organisations. The study was published in peer-reviewed medical journal Nature Genetics.

What kind of research was this?

This genome-wide association study compared the DNA of 2,000 people with Parkinson’s disease to that of healthy controls to determine whether there were any differences between the groups. This type of study is often used to assess the genetic associations of diseases.

What did the research involve?

There were several parts to this study. Initially, 2,000 people with Parkinson’s disease were recruited from several clinics in Oregon, Washington, Georgia and New York. The researchers also selected 1,986 controls (people without the disease) from the same population and geographical region as the cases.

The DNA of both groups were then profiled and compared to identify any genetic variants that were more common in the group with Parkinson’s disease. As is usual with these study designs, the researchers then attempted to replicate their findings in independent samples. This analysis was repeated in another two separate samples.

The researchers then discuss the potential biological reasons for the associations between the genetic elements and the disease.

What were the basic results?

The results confirmed some already known associations between Parkinson’s disease and two genetic regions, SNCA and MAPT. In addition, the research uncovered a new genetic variant called “rs3129882” that was associated with Parkinson’s disease. The variant lies in the HLA genetic region on chromosome 6. This part of the genome is involved in the production of proteins that assist the body’s immune system by recognising invading substances such as bacteria and viruses.

How did the researchers interpret the results?

The researchers conclude that their study has confirmed some known associations and detected a new association between another single-letter variation of the genetic code (SNP) in the HLA region of the genetic code and Parkinson’s disease. Given that there are some immune-related features found in the brains of people with Parkinson’s disease, the genetic association is biologically plausible and supports the involvement of the immune system. The researchers conclude that these “offer new targets for drug development”.


This study appears to be well-conducted, reliable research that furthers our understanding of this complex disease. Although other studies have identified several genetic risk factors for Parkinson’s, and this new association has only a “modest effect on Parkinson’s disease risk”, when considered together the cumulative effect is thought to be substantial.

The identified SNP was in a non-coding region of the genetic code, which means that it does not directly produce proteins itself, but interacts with the genetic code in some other way. There are four major regions that have now been associated with the disease (eight potential variants) and people who have four of the variants are at about double the risk for Parkinson’s compared to those who have only one or none of the variants. It should be pointed out that the absolute risk of developing Parkinson’s is actually quite small and even having all of these variants does not mean a person will get definitely the disease.

Dr Kieran Breen, director of research at Parkinson’s UK, has put these findings in the context of other work, saying "This research, combined with Parkinson's UK funded research at Oxford University into the role of inflammation, may lead to the development of new drug treatments for the condition."

Other points of interest:

  • The researchers note that the people in the control group were on average 12 years older than those with Parkinson’s. However, they say this disparity between the groups is actually a strength as it lowers the likelihood that the controls were too young to have had symptoms.
  • A further strength of the study is the adjustment in the analyses for several factors that may be confounders in the association between genes and Parkinson’s disease, including age, gender and Jewish and European ancestry.

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