Can Parkinson’s be inherited?

Parkinson’s is often described as an ‘idiopathic’ condition — which means it has no known cause. But we now know there are a range of genetic factors that can be involved. In this blog, we explore how the genes we inherit can play a role in Parkinson’s.

We’re still building a picture of why people get Parkinson’s, but understanding the pieces of this complex puzzle will help us unlock better treatments and, one day, a cure.

It is 20 years since researchers uncovered the first genetic variant linked to Parkinson’s. In 1997, the discovery of a family in Italy who had an inherited form of the condition, caused by a single genetic change, sent shockwaves through the research community.

Since that defining moment, a steady stream of new genetic discoveries has transformed our understanding of the condition.

How our genes make us who we are

The human genome contains 23,000 genes — because we have two copies of each that’s 46,000 in total. These genes act as the blueprint that makes us. We all share the same basic blueprint but there are subtle variations that make each individual’s genome unique. These differences in our genes are what make us all different.

Most of these variations are harmless but sometimes a gene has a difference that means the protein it produces does not work as well as it should. These genetic differences are called variants or mutations and can increase the risk of particular illnesses.

Illnesses that are directly caused by inheriting a change in a single gene are very rare. Like most of our characteristics, our health is generally the result of a mixture of different genes coupled with other factors like diet and exercise.


Parkinson’s, genes and inheritance — what we know so far

Parkinson’s is an ‘idiopathic’ condition, which means that it usually isn’t connected to any particular cause. However, for a small minority, Parkinson’s can be caused by inherited changes in genes. For other people, genetic variations can play a part in increasing the risk of the condition.

It’s a complex and changing picture but, so far, changes in around 10 different genes have been linked to different effects on the risk of Parkinson’s.

Let’s take a closer look.

Very rare changes with strong effects

Around 1 in 1,000 people with Parkinson’s carry a very rare change in a gene that causes the condition directly.

With some of these genes inheriting just one copy of the changed gene is enough to cause the condition directly, but in many cases two faulty copies are required (one from each parent).

Changes have been identified in genes including alpha synuclein, parkin, PINK1, DJ-1, ATP13A2, PLA2G6, FBXO7 and VPS35, and often cause the condition to develop at a young age.

More common changes with weaker effects

As well as single genetic changes that directly cause the condition, we now know that there are also changes that increase risk to a lesser extent.

These changes are more common but their effects are more subtle. Inheriting one of them means you are more likely to develop Parkinson’s than someone with the ‘normal’ form of the gene — but this increase in risk is much more subtle, and does not mean you will develop the condition.

Two of the most common genes known to affect risk of Parkinson’s in this way are LRRK2 and GBA.

LRRK2
A change in the LRRK2 gene known as G2019S is probably the most common genetic variant linked to Parkinson’s. In the UK, around 1 in 100 people with Parkinson’s carry this version of the gene although it’s more common in North African and Ashkenazi Jewish populations.

People who inherit a copy of this version of the gene from one of their parents have an increased risk of developing Parkinson’s. Different studies have come up with different answers regarding how much inheriting the G2019S increases risk. One of the most recent studies estimates that people with this form of the LRRK2 gene have between a 25% to 42.5% of developing Parkinson’s by the age of 80.

GBA
The GBA gene was first linked to Parkinson’s in 2004 when doctors noticed that patients with a rare genetic disorder called Gaucher’s disease often had relatives with Parkinson’s.

Gaucher’s is caused by inheriting two faulty copies of the GBA gene, one from each parent. Research has shown that people who inherit just one faulty copy of GBA are more likely to develop Parkinson’s than the general population but again, how much inheriting an altered form of the GBA gene increases risk is still unclear.

Some studies suggest that people who inherit one of the altered forms of GBA have around a 30% chance of being diagnosed by the age of 80. But others estimate the risk to be much lower — 2.2% by age 65 and 10.9% by age 85.

Research is continuing to help us identify more genetic factors that may play a part in the development of Parkinson’s, and to better understand the genes we already know about. The picture is far from complete but it is giving us vital new insights that are revolutionising our understanding of the condition and paving the way for new treatments.

Professor John Hardy discusses his research into inherited forms of Parkinson’s