Multiple phenotype association tests using summary statistics in genome-wide association studies.

TitleMultiple phenotype association tests using summary statistics in genome-wide association studies.
Publication TypeJournal Article
Year of Publication2018
AuthorsLiu, Z, Lin, X
JournalBiometrics
Volume74
Issue1
Pagination165-175
Date Published2018 03
ISSN1541-0420
KeywordsAnalysis of Variance, Computer Simulation, Genome-Wide Association Study, Humans, Linear Models, Lipids, Models, Genetic, Phenotype
Abstract

We study in this article jointly testing the associations of a genetic variant with correlated multiple phenotypes using the summary statistics of individual phenotype analysis from Genome-Wide Association Studies (GWASs). We estimated the between-phenotype correlation matrix using the summary statistics of individual phenotype GWAS analyses, and developed genetic association tests for multiple phenotypes by accounting for between-phenotype correlation without the need to access individual-level data. Since genetic variants often affect multiple phenotypes differently across the genome and the between-phenotype correlation can be arbitrary, we proposed robust and powerful multiple phenotype testing procedures by jointly testing a common mean and a variance component in linear mixed models for summary statistics. We computed the p-values of the proposed tests analytically. This computational advantage makes our methods practically appealing in large-scale GWASs. We performed simulation studies to show that the proposed tests maintained correct type I error rates, and to compare their powers in various settings with the existing methods. We applied the proposed tests to a GWAS Global Lipids Genetics Consortium summary statistics data set and identified additional genetic variants that were missed by the original single-trait analysis.

DOI10.1111/biom.12735
Alternate JournalBiometrics
PubMed ID28653391
PubMed Central IDPMC5743780
Grant ListR35 CA197449 / CA / NCI NIH HHS / United States
U19 CA203654 / CA / NCI NIH HHS / United States
R01 HL113338 / HL / NHLBI NIH HHS / United States
P01 CA134294 / CA / NCI NIH HHS / United States
U01 HG009088 / HG / NHGRI NIH HHS / United States