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The overall goal of this study is to identify and localize the genetic loci and ultimately characterize the genes that explain inter-individual variation in breast density, one of the strongest but perhaps least understood breast cancer risk factors. The two-part hypothesis underlying our study is that (a) there may be increased power to localize and identify breast cancer-related susceptibility genes by examining the genetics of a more proximal but closely related phenotypic endpoint and that (b) there exist genes with strong enough effects on breast density to be detected by linkage analysis. The foundation of our approach is the variance-component method of quantitative trait linkage analysis, whereby information regarding the location of quantitative trait loci is derived from correlations between the quantitative trait in related individuals and genetic markers distributed throughout the genome. Because this approach works best when data can be collected on large, extended families, we are conducting this study in the Old Order Amish of Lancaster County, Pennsylvania, one of oldest and most densely populated Amish settlements in the world.
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