title: Family-based tests applied to extended pedigrees identify rare variants related to hypertension.
abstract: The application of family-based tests to whole-genome sequenced data provides a new window on the role of rare variant alleles in the etiology of disease. By applying family-based tests to these data, we can now identify rare variants associated with disease. Approaches for common variants, by contrast, require large sample sizes for power, and are powerless when faced with rare variants. When we tested Yip et al's 2011 family-based association tests for rare variants on pedigrees from the Genetic Analysis Workshop 18, we found that weighted collapsing methods generally have more power than unweighted methods, but are more prone to type I errors. We then evaluated a sliding window modification of the weighted family-based association tests for rare variants method. Although this modification inflates the rate of false positives, it significantly increases the power of family-based association tests for rare variants to identify causal rare variants.
authors.affiliation: Division of Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Building 35, Room 3A 1000, 35 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Xu
authors.affiliation: Division of Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Building 35, Room 3A 1000, 35 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Harold Z
authors.initials: HZ
authors.lastname: Wang
authors.affiliation: Division of Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Building 35, Room 3A 1000, 35 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: Division of Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Building 35, Room 3A 1000, 35 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Haide
authors.initials: H
authors.lastname: Qin
authors.affiliation: Division of Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Building 35, Room 3A 1000, 35 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Yin Y
authors.initials: YY
authors.lastname: Shugart