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Nature Versus Nurture: What Causes PD?
Juliette Harris, Ph.D., M.S., C.G.C.
A marked change has occurred over the last decade in our understanding of the role of genetics in the causes of Parkinson's disease (PD). For many years, PD was considered to be a "sporadic" disease with no hereditary involvement. Then, beginning about a decade ago, intensive studies led to the discovery of a number of genes that play a role in the development of PD. There is now a consensus that PD, like heart disease, diabetes and Alzheimer's disease, is a "multifactorial" or "complex" disease that is caused by a mixture of environmental and genetic-susceptibility factors. This means that the cause of PD for most people is not found in genes or the environment alone, but in some interaction between them.
Environmental factors that can affect one's health include any influence exerted on the body after conception. These can include any events during fetal development and after birth - such as physical trauma, exposure to chemicals and infections, and nutrition. Some studies, but not all, indicate that pesticide use, rural living and the drinking of well water - all factors that increase exposure to pesticides - contribute to the development of PD. Pesticides are thought to adversely affect the brain by inhibiting energy production resulting in brain cell death. Studies have also shown that smoking and caffeine use appear to protect against the development of PD. However, it is universally agreed that the health risks associated with smoking are worse than any incidental benefits that might be gained by this habit.
Genetic factors that can affect one's health are determined by our genetic make-up at conception and cause differences in the way our bodies work and respond to environmental factors. Scientists have learned about the role of genetic factors in PD by comparing groups of people with and without the disease, from twin studies and by studying a few rare families in which PD is "highly" genetic. In addition to showing that PD is a "complex" disease, studies have revealed that there may be more of a genetic basis to young-onset PD (that is, the 10 percent or so of people with Parkinson's for whom onset occurs at or before age 50) than to later-onset PD. Another view is that there may simply be different genes, or combinations of genes associated with early and late-onset PD.
Further proof that PD is a "complex" disease with both genetic and environmental components comes from studies showing that close relatives of a 70-year-old who has the disease have a two to three percent risk of developing PD, as compared to a one percent risk in the general population. This suggests that small genetic influences are at play in the development of PD. Another indication that PD has a demonstrable, though small, genetic component is that 10 to 15 percent of people with PD report that another family member has PD.
Genetic research studies over the past seven years have uncovered a total of 10 genes associated with PD. For most cases of PD, however, these genes are not thought to play a role. Small as their role may be, genes provide a crucial opportunity for us to study how the brain works. Genetic diseases occur when important genes contain mutations, which result in abnormal proteins that in turn cause disease. Below is a list of ten genes that have been found to be associated with PD. The first have already been identified and characterized. For the other four, PARK3, 9, 10 and 11, the approximate location has been found and research continues to try to identify their exact whereabouts and function.
PD and genetic testing
Most of the genes in the table were identified in families with rare genetic forms of PD. They are not thought to play a role in the development of most cases of PD. Therefore, genetic testing in the general PD population - at the current stage of scientific knowledge - is not going to be helpful. Researchers are still trying to determine which genetic factors contribute to the development of PD for the average patient. This is a very challenging task because we suspect that the interaction of genes with each other and with the environment is probably unique to each individual. Until we gain this level of knowledge, we are a long way off from being able to offer the public PD genetic testing and accurate risk information for family members.
PD genetics and the future
The recent identification of genes that cause PD in a small group of PD families is helping us to understand the processes that lead to the development of PD. Future re-search will undoubtedly reveal additional PD-associated genes and susceptibility factors, which will help us to further understand the cause of PD and lead to better diagnosis and treatment.
If you are interested in participating in genetic research, please visit www.PDtrials.org. One study that is currently enrolling patients is a multi-site study funded by the NIH and directed by Karen Marder, M.D., MPH, of Columbia University. The aim of the study is to identify genetic and environmental risk factors that contribute to the development of young-onset PD. To be eligible, a person must have a diagnosis of PD (by a neurologist) with the onset of symptoms at age 50 or younger. For more information about the study, please call Juliette Harris or Helen Mejia at (212) 305-9183, or email firstname.lastname@example.org or email@example.com.
Juliette Harris, Ph.D., M.S., C.G.C, is the Genetic Counselor at the Division of Movement Disorders at Columbia University. Her research is focused on understanding the genetics of Parkinson's disease.