title: Comparing baseline and longitudinal measures in association studies.
abstract: In recent years, longitudinal family-based studies have had success in identifying genetic variants that influence complex traits in genome-wide association studies. In this paper, we suggest that longitudinal analyses may contain valuable information that can enable identification of additional associations compared to baseline analyses. Using Genetic Analysis Workshop 18 data, consisting of whole genome sequence data in a pedigree-based sample, we compared 3 methods for the genetic analysis of longitudinal data to an analysis that used baseline data only. These longitudinal methods were (a) longitudinal mixed-effects model; (b) analysis of the mean trait over time; and (c) a 2-stage analysis, with estimation of a random intercept in the first stage and regression of the random intercept on a single-nucleotide polymorphism at the second stage. All methods accounted for the familial correlation among subjects within a pedigree. The analyses considered common variants with minor allele frequency above 5% on chromosome 3. Analyses were performed without knowledge of the simulation model. The 3 longitudinal methods showed consistent results, which were generally different from those found by using only the baseline observation. The gene CACNA2D3, identified by both longitudinal and baseline approaches, had a stronger signal in the longitudinal analysis (p = 2.65 × 10(-7)) compared to that in the baseline analysis (p = 2.48 × 10(-5)). The effect size of the longitudinal mixed-effects model and mean trait were higher compared to the 2-stage approach. The longitudinal results provided stable results different from that using 1 observation at baseline and generally had lower p values.
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue 3rd floor, Boston, MA 02118, USA.
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue 3rd floor, Boston, MA 02118, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue 3rd floor, Boston, MA 02118, USA.
authors.forename: Julius
authors.initials: J
authors.lastname: Ngwa
authors.affiliation: Département de Mathématiques, Université de Sherbrooke, Québec, Canada J1K 2R1.
authors.forename: Catherine
authors.initials: C
authors.lastname: Allard
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue 3rd floor, Boston, MA 02118, USA.
authors.forename: Ching-Ti
authors.initials: CT
authors.lastname: Liu
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue 3rd floor, Boston, MA 02118, USA.
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples