AUTHOR=Vujkovic Marijana , Aplenc Richard , Alonzo Todd A. , Gamis Alan S. , Li Yimei TITLE=Comparing Analytic Methods for Longitudinal GWAS and a Case-Study Evaluating Chemotherapy Course Length in Pediatric AML. A Report from the Children's Oncology Group JOURNAL=Frontiers in Genetics VOLUME=7 YEAR=2016 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2016.00139 DOI=10.3389/fgene.2016.00139 ISSN=1664-8021 ABSTRACT=
Regression analysis is commonly used in genome-wide association studies (GWAS) to test genotype-phenotype associations but restricts the phenotype to a single observation for each individual. There is an increasing need for analytic methods for longitudinally collected phenotype data. Several methods have been proposed to perform longitudinal GWAS for family-based studies but few methods are described for unrelated populations. We compared the performance of three statistical approaches for longitudinal GWAS in unrelated subjectes: (1) principal component-based generalized estimating equations (PC-GEE); (2) principal component-based linear mixed effects model (PC-LMEM); (3) kinship coefficient matrix-based linear mixed effects model (KIN-LMEM), in a study of single-nucleotide polymorphisms (SNPs) on the duration of 4 courses of chemotherapy in 624 unrelated children with