twin environment is only controlled for approximately the first 20 years of life, confounding the interpretation of the environmental and gene-environmental contributions to the disease. Furthermore, most familial PD demonstrates age-dependent penetrance, making misclassification of phenotype possible without longitudinal follow-up of subjects. Early twin studies reporting concordance of MZ twins (11,12) were not supported in larger nonpopulation-based series (13,14). Subsequently, several population-based twin studies have found no difference in concordance between MZ and DZ twins in Finnish (15), Swedish (16), and American (17) populations. In one of these studies (17), the relative risk of PD in MZ twins was 6.0 for those with age at onset less than 50. However, these findings were based upon four concordant MZ, two concordant DZ, no discordant MZ, and 10 discordant DZ twins. Although these numbers are small, these findings are consistent with the family and linkage studies in which genetic contributions appear to be more common in younger-onset cases.
Another technique to determine the relative importance of genetic and environmental influences in the etiology of PD utilizes detailed knowledge of genealogies to calculate a kinship coefficient. The kinship coefficient is defined as the probability that two alleles at the same locus, drawn at random (one from each person), are identical by descent, providing a measure of the degree of relatedness between two individuals. A large study of an Icelandic genetic database found that subjects with PD were significantly more related to each other than controls from the same population (18) leading to the discovery of the PARK10 locus (19). However, the findings of this study are population-specific and may not translate to other populations. For example, using the same methods, a recent study (20) in an Amish community found that subjects with PD were less related to each other than subjects without the evidence of PD. The authors concluded that adult environmental factors are the likely cause of PD in this community.
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