title: Data for Genetic Analysis Workshop 18: human whole genome sequence, blood pressure, and simulated phenotypes in extended pedigrees.
abstract: Genetic Analysis Workshop 18 (GAW18) focused on identification of genes and functional variants that influence complex phenotypes in human sequence data. Data for the workshop were donated by the T2D-GENES Consortium and included whole genome sequences for odd-numbered autosomes in 464 key individuals selected from 20 Mexican American families, a dense set of single-nucleotide polymorphisms in 959 individuals in these families, and longitudinal data on systolic and diastolic blood pressure measured at 1-4 examinations over a period of 20 years. Simulated phenotypes were generated based on the real sequence data and pedigree structures. In the design of the simulation model, gene expression measures from the San Antonio Family Heart Study (not distributed as part of the GAW18 data) were used to identify genes whose mRNA levels were correlated with blood pressure. Observed variants within these genes were designated as functional in the GAW18 simulation if they were nonsynonymous and predicted to have deleterious effects on protein function or if they were noncoding and associated with mRNA levels. Two simulated longitudinal phenotypes were modeled to have the same trait distributions as the real systolic and diastolic blood pressure data, with effects of age, sex, and medication use, including a genotype-medication interaction. For each phenotype, more than 1000 sequence variants in more than 200 genes present on the odd-numbered autosomes individually explained less than 0.01-2.78% of phenotypic variance. Cumulatively, variants in the most influential gene explained 7.79% of trait variance. An additional simulated phenotype, Q1, was designed to be correlated among family members but to not be associated with any sequence variants. Two hundred replicates of the phenotypes were simulated, with each including data for 849 individuals.
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, 78227, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, 78227, USA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dyer
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, 78227, USA.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Peralta
authors.affiliation: Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, 48109, USA.
authors.forename: Goo
authors.initials: G
authors.lastname: Jun
authors.affiliation: Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Wood
authors.affiliation: Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, 48109, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Fuchsberger
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, 78227, USA.
authors.forename: Marcio A
authors.initials: MA
authors.lastname: Almeida
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, 78227, USA.
authors.forename: Jack W
authors.initials: JW
authors.lastname: Kent
authors.affiliation: Division of Clinical Epidemiology, Department of Medicine, University of San Antonio Health Science Center at San Antonio, San Antonio, Texas, 78229, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Fowler
authors.affiliation: Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, 48109, USA.
authors.forename: Tom W
authors.initials: TW
authors.lastname: Blackwell
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, 78227, USA.
authors.forename: Sobha
authors.initials: S
authors.lastname: Puppala
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, 78227, USA.
authors.forename: Satish
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, 78227, USA.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Curran
authors.affiliation: Division of Clinical Epidemiology, Department of Medicine, University of San Antonio Health Science Center at San Antonio, San Antonio, Texas, 78229, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Lehman
authors.affiliation: Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, 48109, USA.
authors.forename: Goncalo
authors.initials: G
authors.lastname: Abecasis
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, 78227, USA.
authors.forename: Ravindranath
authors.initials: R
authors.lastname: Duggirala
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, 78227, USA.
authors.forename: John
authors.initials: J
authors.lastname: Blangero