title: Genomic screening in family-based association testing.
abstract: Due to the recent gains in the availability of single-nucleotide polymorphism data, genome-wide association testing has become feasible. It is hoped that this additional data may confirm the presence of disease susceptibility loci, and identify new genetic determinants of disease. However, the problem of multiple comparisons threatens to diminish any potential gains from this newly available data. To circumvent the multiple comparisons issue, we utilize a recently developed screening technique using family-based association testing. This screening methodology allows for the identification of the most promising single-nucleotide polymorphisms for testing without biasing the nominal significance level of our test statistic. We compare the results of our screening technique across univariate and multivariate family-based association tests. From our analyses, we observe that the screening technique, applied to different settings, is fairly consistent in identifying optimal markers for testing. One of the identified markers, TSC0047225, was significantly associated with both the ttth1 (p = 0.004) and ttth1-ttth4 (p = 0.004) phenotype(s). We find that both univariate- and multivariate-based screening techniques are powerful tools for detecting an association.
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA. amurphy@hsph.harvard.edu
authors.forename: Amy
authors.initials: A
authors.lastname: Murphy
authors.forename: Matthew B
authors.initials: MB
authors.lastname: McQueen
authors.forename: Jessica
authors.initials: J
authors.lastname: Su
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Ross
authors.initials: R
authors.lastname: Lazarus
authors.forename: Nan M
authors.initials: NM
authors.lastname: Laird
authors.forename: Christoph
authors.initials: C
authors.lastname: Lange
authors.forename: Kristel
authors.initials: K
authors.lastname: Van Steen
mesh_terms: D005190:Family; D005820:Genetic Testing; D015894:Genome, Human / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D010641:Phenotype