Twins

An example of the use of investigations in twins to understand more about a disease is provided by recent work in Parkinson's disease. Parkinson's disease (PD) is a progressive neurodegenerative disease causing slowness, tremor, and problems with walking and balance. PD is rare before age fifty but becomes more common thereafter, with increasing age. The cause of PD has long been debated. Both genetic and environmental causes have been suggested, but neither has been definitively shown. Researchers turned to studies in twins to determine the relative contribution of genes and environment to the disease.

The first studies identified twin pairs by recruiting through physicians and PD patient organizations. Studies in the United States, the United Kingdom, and Germany identified 103 pairs, of which only thirteen were concordant for PD. In Finland, forty-two twins with PD were identified by records linkage, but among these was only one concordant pair—a DZ pair. No study had convincingly demonstrated greater monozygotic than dizygotic concordance for the disease, and in all studies the preponderance of twin pairs were discordant for disease. These findings supported an environmental cause of PD. Nonetheless, the advent of molecular genetics prompted great interest in investigations of genetic causes of disease and prompted the resurgence of the hypothesis that all PD had a genetic cause. To address this, a study in a large, unselected cohort—the National Academy of Sciences/National Resource Council (NAS/NRC) World War II Veteran Twins Registry—was undertaken.

In the mid-1950s, the Medical Follow-up Agency of the Institute of Medicine of the NAS/NRC established a registry of approximately 32,000 Caucasian male twins, all of whom were born between 1917 and 1927 and were veterans of the U.S. Armed Services. In all, 161 twin pairs were identified, twenty-one of which were concordant for PD, as shown in Table 2. In those few pairs with early-onset PD, concordance was greater in MZ pairs. In those with more typical PD, beginning after age fifty, there was no difference in MZ and DZ concordance.

These findings suggest a strong genetic determinant for early-onset disease but predominantly environmental causes in more typical late-onset disease. One caveat is the narrow age range of the twins, who were sixty-seven to seventy-seven years old when studied. Since PD is a late-life disorder, PD in some twins may have been missed with an examination at only one time point. To overcome this, a second evaluation is in progress.