Twin Studies: Solvent Exposure, Parkinson’s Disease and Gender Identity Disorder
What do twins tell us about environmental chemicals?
Posted Mar 15, 2012
The medical and psychological literature includes many twin studies. I recently came across two of particular interest: the first on the possible link between solvent exposure and Parkinson's disease, and the second on genetic and environmental influences on gender identity disorder. More can be found on these two topics in my forthcoming article in the journal, Twin Research and Human Genetics. Also, please visit my new website (www.drnancysegaltwins.org) for information about my books on twins and other twin-related material.
The possible health risks posed by solvents and other chemical substances in our occupational and recreational environments have been of concern. Parkinson's disease is a progressive degenerative disorder of the nervous system affecting movement and other body functions (Mayo Clinic, 2012). It has attracted considerable interest, given hypothesized associations with exposed to various hazardous environmental materials. Substantiating that view is that past twin studies of Parkinson's disease have failed to find compelling evidence of genetic effects when the illness was diagnosed after age fifty (Tanner, Ottman, Goldman, Ellenberg, Chan, Mayeux, and Langston, 1999). However, when at least one twin's age at onset was fifty or younger, then genetic factors appeared to play a role.
An interdisciplinary team of investigators from the United States and Canada conducted the first population-based study of possible associations between solvent exposure and Parkinson's disease (Goldman, Quinlan, Ross, Marras, Meng, Bhudhikanok, et al, 2012). Rather than rely on case-control methods in which genetic end environmental factors could not be controlled completely, the researchers gained access to MZ twins discordant for the disease. A comparison sample of discordant DZ twins was also available for study.
The sample included 198 disease-discordant male twin pairs. Affected twins and their twin brothers were evaluated in person by a specialist in movement disorders that included a videotaped neurological examination. Twins' medical records were also inspected. Based on all available information, the diagnosis of Parkinson's disease was made by two separate neurologists.
Twins also completed detailed questionnaires determine their life time exposure to six different solvents, namely n-hexane, xylene, toluene, carbon tetrachloride (CCI4), trichloroethylene (TCE) and percholomethylene (PERC). However, this information was gathered indirectly because most individuals are unaware of the specific chemical substances in their environments. This task was accomplished by administering a detailed occupational exposure assessment that had been developed previously for cancer research. The nature and degree of solvent exposure was then inferred for each job, based on the twins' occupational histories. Twins additionally indicated their histories of smoking and head injuries.
Across the entire sample the proportion of pairs with at least one exposed twin was greatest for toluene (27%) and lowest for PERC (6%). Individuals holding jobs as cabinet makers, artists, mechanics, electricians and carpenters were those most likely to have been exposed to toluene. However, in 48% of the pairs either one or both twins had been exposed to at least one or more of the six specified solvents. Risk for Parkinson's disease was highest for individuals exposed to the combination of TCE or PERC. However, risk was modestly (albeit, not significantly) elevated if there was exposure to any of the six solvents, or any of the four excluding PERC and TCE. Solvent exposure was not associated with the age at diagnosis of Parkinson's disease, but the investigators noted that they had little statistical power to assess this relationship.
This important study raises key concerns for the general public. For example, TCE, PERC and CCI4 have been used widely for many years. TCE is used in dry cleaning and degreasing and has been an additive in many household products such as typewriter correction fluid and spot removers. TCE has been detected in air, soil and human breast milk. Of course, replication of the study using other samples will be the next step. The retrospective and indirect nature of the study also mandates that prospective and direct analyses be conducted. The investigators noted these limitations of their study.
An unanswered question that the investigators should have addressed was whether the MZ twin pairs showed greater concordance for solvent exposure and Parkinson's disease risk than the DZ twin pairs. It is also unclear why the analyses combined the MZ and DZ twin pairs--the introductory section indicates that because twins are "genetically very similar or identical, and share many demographic and lifestyle factors, discordant twin-pair designs are more resistant to confounding factors than typical case-control study designs" (p. 1-2). That is true, of course, but only for MZ twins. DZ twins may differ considerably with reference to their genetically based disease predispositions and life style choices that might eventuate in different job choices and unequal solvent exposure. Disease discordance in MZ and DZ twins might, therefore, have different underlying factors. It is possible that an unknown proportion of discordant DZ twin pairs resulted from the co-twins' different genetic predispositions and had little to do with their different degrees of solvent exposure. Nevertheless, this study deserves to be read in full and the results taken seriously.
Gender Identity in Twins
A recent review of case reports documenting GID in one or both MZ and DZ co-twins has been undertaken by researchers in Belgium and Canada (Heylens, De Cuypere, Zucker, Schelfaut, Elaut, Vanden Bosche, et al. (2012). A significant difference in GID concordance was found between the MZ (39.1%) and same-sex DZ (0%) twin pairs (p< .005). Furthermore, none of the opposite sex-twin pairs was concordant. These findings show that genetic factors effect individual differences in GID. This paper includes insightful discussion of GID and excerpts from the life histories of selected sets.
References for Further Reading
Heylens, G., De Cuypere, G., Zucker, K.J., Schelfaut, C., Elaut, E., Vanden Bosche, H., et al. (2012). Gender identity disorder: A review of the case report literature. Journal of Sexual Medicine, 9, 751-757.
Mayo Clinic (11, March 2012). Parkinson's disease. http://www.mayoclinic.com/health/parkinsons-disease/DS00295.
Goldman, S.M., Quinlan, P.J., Ross, W., Marras, C., Meng, C., Bhudhikanok, G.S. et al. (2011). Solvent exposure and Parkinson disease risk in twins. Annals of Neurology, DOI: 10.1022/ana.22629.
Tanner, C.M., Ottman, R., Goldman, S., Ellenberg, J., Chan, P., Mayeux, R. & J. W.,