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Genetic Linkage

Twin Study Supports Parkinson’s-Solvent Link

In this age of genome sequencing, it’s refreshing to read about the continuing power of a simple tool of genetics: the twin study. But in reporting a new study linking long-term exposure to certain solvents to raised risk of Parkinson’s disease (PD), the media missed the subtle value of a twin study.

Samuel Goldman, MD, MPH and Caroline Tanner, MD, PhD, of the Parkinson’s Institute in Sunnyvale, California and their colleagues interviewed 49 identical and 50 fraternal pairs of twins in which one had PD, probing lifetime exposure to six chemicals that case reports had previously associated with PD. The participants came from the National Academy of Sciences/National Research Council World War II Veteran Twins Cohort, with average age 66 at diagnosis, and symptoms starting 10 to 40 years after exposure began. The researchers found that long-term exposure to trichloroethylene (TCE) increases risk sixfold and long-term exposure to either TCE or another solvent, perchloroethylene (PERC), increases risk ninefold, in both identical and fraternal twins.

Because twin type didn’t influence whether or not a person developed PD, but solvent exposure did, many media reports lumped the twin types together. But in terms of genes shared, the two are not alike.

Fraternal (dizygotic) twins share on average 50% of their gene variants, while identical (monozygotic) twins share 100%. So if a trait or illness is largely inherited, the percentage of identical twin pairs in which both are affected exceeds the percentage for fraternal twins. But if both members are affected in about equal percentages of both twin types, then the trait or illness is more heavily influenced by something in the environment – such as organic solvents.

In the new study, which used a variation on the twin study theme, the comparison of the two types is still important, because it suggests that the ability of these chemicals to harm the dopamine-producing neurons in the substantia nigra isn’t the consequence of an inherited susceptibility. Rather, it can happen to anyone. But it’s easy to see why this fact didn't make it into the NIH news release about the report, for the study itself barely mentions it, sandwiching the significance of twin type, hobby-related exposure, head injury, or smoking into one sentence (with “data not shown") between the results and discussion.

The lack of a genetic link is, in a way, bad news, for the suspect chemicals are ubiquitous in the environment, and they persist. And unlike a disorder such as berylliosis, in which inherited sensitivity to the alkaline earth metal beryllium causes lung disease, we're all at risk for PD from exposure to certain solvents. But discovering threshold levels will be important.

Electricians, dry cleaners, and industrial machine repair specialists are the most likely to encounter high levels of TCE for long periods. The chemical is also found, in lower concentrations, in air, soil, food (including breast milk), and in 30% of drinking water supplies in the U.S., where some 50 million pounds enter the environment each year. TCE is also in various adhesives, spot removers, carpet cleaners, and paints. Before a 1977 ban from the Food and Drug Administration, it was used to decaffeinate coffee, disinfect skin, fumigate grain, and as a general anesthetic, and was removed from “liquid paper” products in 2009. Further studies are needed to measure and compare levels of everyday exposure to those that could have contributed to causing PD in the affected twins with high exposures.

Because fewer than 10 percent of Parkinson’s cases are inherited, identifying environmental triggers is crucial, and the implication of widely-used industrial and household chemicals disturbing.

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