Phenome-wide Association Study Relating Pretreatment Laboratory Parameters With Human Genetic Variants in AIDS Clinical Trials Group Protocols.

TitlePhenome-wide Association Study Relating Pretreatment Laboratory Parameters With Human Genetic Variants in AIDS Clinical Trials Group Protocols.
Publication TypeJournal Article
Year of Publication2015
AuthorsMoore CB, Verma A, Pendergrass S, Verma SS, Johnson DH, Daar ES, Gulick RM, Haubrich R, Robbins GK, Ritchie MD, Haas DW
JournalOpen Forum Infect Dis
Volume2
Issue1
Paginationofu113
Date Published2015 Jan
ISSN2328-8957
Abstract

Background.  Phenome-Wide Association Studies (PheWAS) identify genetic associations across multiple phenotypes. Clinical trials offer opportunities for PheWAS to identify pharmacogenomic associations. We describe the first PheWAS to use genome-wide genotypic data and to utilize human immunodeficiency virus (HIV) clinical trials data. As proof-of-concept, we focused on baseline laboratory phenotypes from antiretroviral therapy-naive individuals. Methods.  Data from 4 AIDS Clinical Trials Group (ACTG) studies were split into 2 datasets: Dataset I (1181 individuals from protocol A5202) and Dataset II (1366 from protocols A5095, ACTG 384, and A5142). Final analyses involved 2547 individuals and 5 954 294 imputed polymorphisms. We calculated comprehensive associations between these polymorphisms and 27 baseline laboratory phenotypes. Results.  A total of 10 584 (0.17%) polymorphisms had associations with P < .01 in both datasets and with the same direction of association. Twenty polymorphisms replicated associations with identical or related phenotypes reported in the Catalog of Published Genome-Wide Association Studies, including several not previously reported in HIV-positive cohorts. We also identified several possibly novel associations. Conclusions.  These analyses define PheWAS properties and principles with baseline laboratory data from HIV clinical trials. This approach may be useful for evaluating on-treatment HIV clinical trials data for associations with various clinical phenotypes.

DOI10.1093/ofid/ofu113
Alternate JournalOpen Forum Infect Dis
PubMed ID25884002
PubMed Central IDPMC4396430
Grant ListU01 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069419 / AI / NIAID NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069439 / AI / NIAID NIH HHS / United States