Genetic, Transcriptomic, and Epigenetic Studies of HIV-Associated Neurocognitive Disorder

Levine, Andrew J. PhD*; Panos, Stella E. PhD; Horvath, Steve PhD‡,§

JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0000000000000069
Critical Review: Epidemiology and Prevention
Abstract

Abstract: The Human Genome Project, coupled with rapidly evolving high-throughput technologies, has opened the possibility of identifying heretofore unknown biological processes underlying human disease. Because of the opaque nature of HIV-associated neurocognitive disorder (HAND) neuropathogenesis, the utility of such methods has gained notice among NeuroAIDS researchers. Furthermore, the merging of genetics with other research areas has also allowed for application of relatively nascent fields, such as neuroimaging genomics, and pharmacogenetics, to the context of HAND. In this review, we detail the development of genetic, transcriptomic, and epigenetic studies of HAND, beginning with early candidate gene association studies and culminating in current “omics” approaches that incorporate methods from systems biology to interpret data from multiple levels of biological functioning. Challenges with this line of investigation are discussed, including the difficulty of defining a valid phenotype for HAND. We propose that leveraging known associations between biology and pathology across multiple levels will lead to a more reliable and valid phenotype. We also discuss the difficulties of interpreting the massive and multitiered mountains of data produced by current high-throughput omics assays and explore the utility of systems biology approaches in this regard.

Author Information

*Department of Neurology, National Neurological AIDS Bank, David Geffen School of Medicine, University of California, Los Angeles, CA;

Department of Psychiatry and Biobehavioral Science, David Geffen School of Medicine, University of California, Los Angeles, CA;

Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA; and

§Department of Biostatistics, University of California, Los Angeles, CA.

Correspondence to: Andrew J. Levine, PhD, National Neurological AIDS Bank, David Geffen School of Medicine, University of California, Los Angeles, 11645 Wilshire Blvd, Suite 770, Los Angeles, CA 90025 (e-mail: ajlevine@mednet.ucla.edu).

Supported by Clinical and Translational Science Institute and Center for AIDS Research at UCLA, Grant UL1TR000124 (S.H.); National Institute for Drug Abuse, Grant R01DA030913 (A.L. and S.H.); UCLA AIDS Institute and Center for AIDS Research, Grant AI28697 (A.L); National Institute for Drug Abuse, Grant R03DA026099 (A.L.); and California HIV/AIDS Research Program, Grant ID06-LA-187 (A.L).

The authors have no conflicts of interest to disclose.

Received November 06, 2013

Accepted November 06, 2013

© 2014 by Lippincott Williams & Wilkins