title: Modeling of multivariate longitudinal phenotypes in family genetic studies with Bayesian multiplicity adjustment.
abstract: Genetic studies often collect data on multiple traits. Most genetic association analyses, however, consider traits separately and ignore potential correlation among traits, partially because of difficulties in statistical modeling of multivariate outcomes. When multiple traits are measured in a pedigree longitudinally, additional challenges arise because in addition to correlation between traits, a trait is often correlated with its own measures over time and with measurements of other family members. We developed a Bayesian model for analysis of bivariate quantitative traits measured longitudinally in family genetic studies. For a given trait, family-specific and subject-specific random effects account for correlation among family members and repeated measures, respectively. Correlation between traits is introduced by incorporating multivariate random effects and allowing time-specific trait residuals to correlate as in seemingly unrelated regressions. The proposed model can examine multiple single-nucleotide variations simultaneously, as well as incorporate familyspecific, subject-specific, or time-varying covariates. Bayesian multiplicity technique is used to effectively control false positives. Genetic Analysis Workshop 18 simulated data illustrate the proposed approach's applicability in modeling longitudinal multivariate outcomes in family genetic association studies.
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA ; Department of Pediatrics, University of Cincinnati College of Medicine, 3235 Eden Avenue,Cincinnati, OH 45267, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA ; Department of Pediatrics, University of Cincinnati College of Medicine, 3235 Eden Avenue,Cincinnati, OH 45267, USA.
authors.forename: Brad G
authors.initials: BG
authors.lastname: Kurowski
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Environmental Health, University of Cincinnati College of Medicine, 3223 Eden Avenue, Cincinnati, OH 45267, USA.
authors.forename: Eileen S
authors.initials: ES
authors.lastname: Alexander
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA ; Department of Pediatrics, University of Cincinnati College of Medicine, 3235 Eden Avenue,Cincinnati, OH 45267, USA.
authors.forename: Tesfaye B
authors.initials: TB
authors.lastname: Mersha
authors.affiliation: Department of Biostatistics, University of Kentucky, 725 Rose Street, Lexington, KY 40536, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Fardo
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Valentina V
authors.initials: VV
authors.lastname: Pilipenko
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Leah
authors.initials: L
authors.lastname: Kottyan
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA ; Department of Pediatrics, University of Cincinnati College of Medicine, 3235 Eden Avenue,Cincinnati, OH 45267, USA.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Martin