Environmental factors can confound identification of a major gene effect: Results from a segregation analysis of a simulated population of lung cancer families
✍ Scribed by Thomas A. Sellers; Todd W. Weaver; Brian Phillips; Michael Altmann; Stephen S. Rich
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 42 KB
- Volume
- 15
- Category
- Article
- ISSN
- 0741-0395
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✦ Synopsis
Proper control of environmental factors can be crucial to the identification of genes that influence susceptibility to a complex trait, especially for a trait such as lung cancer, for which the environmental factor (smoking) accounts for a significant etiologic fraction of the disease. An earlier segregation analysis of 337 Louisiana families, which incorporated direct measure of tobacco consumption, provided evidence for autosomal codominant inheritance of a major gene that influenced age at onset of lung cancer. Subsequent analyses were performed in which the families were stratified into two subsets based on birth cohort of the proband; results suggested the presence of heterogeneity that were postulated to reflect the influence of cohort trends in tobacco consumption. To evaluate this hypothesis further, we simulated a population of three-generation pedigrees in which an autosomal dominant mode of susceptibility to lung cancer was transmitted, but tobacco use varied across generations corresponding to published trends in smoking. A total of 200,000 individuals in families of various sizes, ages, and cigarette smoking habits were simulated from 1900 to 1980. From this