Work

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

Year: 2014

Type: article

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.

Source: Open Forum Infectious Diseases

DOI: 10.1093/ofid/ofu113

Authors: Carrie B. Moore, Anurag Verma, Sarah Pendergrass, Shefali S. Verma, Daniel H. Johnson, Eric S. Daar, Roy M. Gulick, Richard Haubrich, Gregory K. Robbins, Marylyn D. Ritchie, David W. Haas

Institutions: Pennsylvania State University, Vanderbilt University, University of California, Los Angeles, The Lundquist Institute, Harbor–UCLA Medical Center, Weill Cornell Medicine, University of California San Diego, Harvard University

Language: English

Topic: Genetic Associations and Epidemiology

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,053

Funders: ACT Government, National Institutes of Health, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Allergy and Infectious Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences

Awards: ADULT AIDS CLINICAL TRIALS UNIT (AACTU), G1050281965, Units for HIV/AIDS Clinical Trials Networks, G1068660208, G1118287939, eMERGE Coordinating Center, G1158968046, G1169301292, G119332616, G1214792496, G1225594167, Stanford AIDS Clinical Trials Unit, G1593133010, WASHINGTON UNIVERSITY AIDS CLINICAL TRIALS UNIT, G16708505, G1678638035, G183157880, G185513119, Vanderbilt HIV Clinical Trials Unit, G1865158448, G1939689254, G1978423557, G2093356446, G2127051194, G2135258891, G2241242742, G2268686290, G232810045, G2370685347, G2394140265, G2501702145, UAB Center for Clinical and Translational Science (CCTS) UL1, G2539633428, G25420283, G2737559749, G2800974659, G2833553957, ADULT AIDS CLINICAL TRIALS UNIT, Cornell Clinical Trials Unit, G3142995538, G3179975197, UCLA Clinical and Translational Science Institute, Johns Hopkins AIDS Clinical Trials Unit, G3441327761, G3483687112, GBV-C effects on CD4 activation and expansion, UW Clinical HIV Integrated Research Program, G3812657198, G3873853564, G3881544606, G390975780, G3922356, ADULT THERAPEUTIC CLINICAL TRIALS PROGRAM FOR AIDS, Philadelphia IMPAACT Clinical Trials Unit, G4099673573, G4649361189, G475936976, G488872913, Case Clinical Trials Unit, University of Pittsburgh Clinical Trials Unit, G5031627105, G5046654427, ADULT THERAPEUTIC CLINICAL TRIALS PROGRAM IN AIDS, Integrated University of Puerto Rico Clinical Trials Unit, G5268332287, The University of Rochester Clinical and Translational Science Institute, G5431849782, ADULT ACTG CENTRAL GROUP, G5469398932, G5588634031, Improving Antiretroviral Management for HIV, G5647179126, UCSD Department of Medicine HIV/AIDS Clinical Trials Unit, Case AIDS Clinical Trials Unit, Philadelphia IMPAACT Clinical Trials Unit, G6186512954, G6270489734, G650174051, UNC Clinical and Translational Science Award, G6615853387, G6643580741, University of Cincinnati AIDS Clinical Trials Unit- UC ACTU, G6687940712, G6812155733, UCSF HIV Clinical Trials Unit, Partners Healthcare Systems/Harvard Medical School/Boston Medical Center AIDS CTU, G7401883790, General Clinical Research Center, The Vanderbilt Institute for Clinical and Translational Research (VICTR), G7807354757, G8397211215, G8487837538, HIV/AIDS Clinical Trials Unit, Institute of Human Virology Clinical Trials Unit, G878552033, G9000072212, San Diego Center for AIDS Research (SD CFAR), Center for AIDS Research at Emory University, The University of North Carolina Center for AIDS Research, Columbia Collaborative HIV/AIDS Clinical Trials Unit, University of North Carolina Global HIV Prevention and Treatment Clinical Trials Unit, G911961363, G926868656, G936311976, G961682679, Colorado Clinical and Translational Science Institute (UL1)

OpenAlex ID: W2133594846

FWCI: 3.168

Cites: 47

Cited by: 36

Related to: 10