Abstract
The twin method for investigating genetic and environmental causes of disease has been applied mostly in early-onset illnesses. Analysis of late- onset disorders requires reexamination of common assumptions about the relation between genetic causes and the degree of concordance expected. This paper considers Alzheimer disease (AD) as an example of a late-onset disorder with putative genetic factors. For argument it employs the strong hypothesis that AD is an autosomal dominant trait with age-dependent expression, as described by a previously published parametric model. That model encompasses 2 principal variants of disease: a rare form with onset in middle life, and a more common late-onset type which is nonetheless eventually fully penetrant. The present work then specifies the probability that, when a given member of a twin pair (the proband) is affected, an identical or fraternal co-twin also shows the disease. Such probability is expressed as a function of the age at onset of the proband and the current age of the pair. Even under strong working assumptions regarding genetic influence, the expected proportion of identical co-twins actually affected with AD will not exceed 40% until the subjects are about 80 years old. Therefore, except in very old subjects, modest twin concordance is a feeble argument against genetic causes, or in favor of exclusively environmental ones. In this sense the interpretation of results of twin studies in AD and other late-onset disorders differs substantially from studies of diseases with early onset.
Original language | English (US) |
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Pages (from-to) | 628-634 |
Number of pages | 7 |
Journal | American journal of medical genetics |
Volume | 44 |
Issue number | 5 |
DOIs | |
State | Published - 1992 |
Externally published | Yes |
Keywords
- age-dependence
- autosomal dominant trait
- concordance
ASJC Scopus subject areas
- Genetics(clinical)