Study Delves Into Genetic, Environmental Risk Factors for Parkinson’s

The interplay between different genetic and environmental factors, from a family history of disease to smoking habits, contributes to Parkinson’s risk and can help in designing tests that better allow for its early detection, a study suggests.

The study, “Parkinson’s disease determinants, prediction and gene–environment interactions in the UK Biobank,” was published in the journal of Neurology, NeuroSurgery & Psychiatry.

Identifying those at risk for, or in early stages of, Parkinson’s disease offer the best opportunities for treatments that effectively prevent, slow, and possibly reverse its progression.

Both environmental and genetic risk factors are known to contribute to Parkinson’s, but how this happens and the degree to which each contributes to disease remain poorly understood.

Researchers at Queen Mary University of London investigated how environmental risk factors associated with a Parkinson’s diagnosis, as well as the interaction of genetic risk with these factors.

The study, funded by the Barts Charity, included 1,276 Parkinson’s patients (median age at diagnosis, 66.1) and 500,406 healthy people serving as controls, all followed for a median of 12 years. Their data were collected from the UK Biobank, a large repository of demographic, lifestyle, and clinical and radiological information, as well as genotyping and health records, on people ages 40 to 69, recruited between 2006 and 2010 from across the U.K.

The team began by determining the association of several risk factors with Parkinson’s, using statistical models adjusted for age, sex, ethnicity, and socioeconomic status.

Strong associations were found between this disease and several well-established risk and protective factors, as well as some new ones.

Risk factors included a family history of the disease, depression, excessive daytime sleepiness, and a family history of dementia, while protective ones were not smoking, and low alcohol consumption (less than one drink per week).

New risk associations were seen for those with epilepsy and earlier menarche (the occurrence of a first menstrual period).

“Whether the association is driven by epilepsy, chronic use of antiepileptic drugs or residual confounding remains to be determined,” the researchers wrote, while the association with earlier menstruation should be interpreted with “caution,” because it counters previous findings “that oestrogens may be neuroprotective.”

Weaker evidence existed between Parkinson’s and a history of peptic (gastric) ulcers or type 2 diabetes (diabetes mellitus). Other factors such as anxiety, body mass index, constipation, pesticide exposure, or coffee consumption was not seen to influence Parkinson’s risk in this group.

Researchers then evaluated the contribution of different combined genetic risk factors, or polygenic risk scores. Higher polygenic risk scores were associated with age at Parkinson’s diagnosis, and individuals with higher scores had a 3.4 times increased risk of developing the disease, compared to those with lower scores.

The team then used a basic risk algorithm, developed in the PREDICT-PD study, and verified if its predictive power would improve with the inclusion of different genetic factors, in the form of polygenic risk scores.

Including these scores did increase the algorithm’s ability to predict Parkinson’s, but by an amount too small to be helpful in clinical use. Still, the researchers believe this approach can be used to enrich populations in group studies of those at higher risk of Parkinson’s.

Finally, researchers evaluated how the interplay between genetic and environmental risk factors could contribute to disease risk. How diabetes related to Parkinson’s risk, they found, appears to depend on background genetic risk. Specifically, diabetes appears to become a more potent risk factor for people without a family history (low genetic risk) of Parkinson’s.

“These results provide further evidence that we can identify a group at higher risk of Parkinson’s disease, who would be ideal candidates for neuroprotective drug trials or other prevention strategies,” Alastair Noyce, MD, PhD, a study author and researcher at Wolfson Institute’s Preventive Neurology Unit, said in a university press release.

“Our research takes a further step forward in thinking about the prevention of Parkinson’s disease and who are the best groups to target for prevention,” Noyce added.