Assessment of rare BRCA1 and BRCA2 variants of unknown significance using hierarchical modeling.

ABSTRACT: Current evidence suggests that the genetic risk of breast cancer may be caused primarily by rare variants. However, while classification of protein-truncating mutations as deleterious is relatively straightforward, distinguishing as deleterious or neutral the large number of rare missense variants is a difficult on-going task. In this article, we present one approach to this problem, hierarchical statistical modeling of data observed in a case-control study of contralateral breast cancer (CBC) in which all the participants were genotyped for variants in BRCA1 and BRCA2. Hierarchical modeling permits leverage of information from observed correlations of characteristics of groups of variants with case-control status to infer with greater precision the risks of individual rare variants. A tot

SUBMITTER: Capanu M 

PROVIDER: S-EPMC3111904 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature