Genome-wide association study of HIV-associated neurocognitive disorder (HAND): A CHARTER group study.

TitleGenome-wide association study of HIV-associated neurocognitive disorder (HAND): A CHARTER group study.
Publication TypeJournal Article
Year of Publication2017
AuthorsJia, P, Zhao, Z, Hulgan, T, Bush, WS, Samuels, DC, Bloss, C, Heaton, RK, Ellis, RJ, Schork, N, Marra, CM, Collier, AC, Clifford, DB, Gelman, B, Sacktor, N, Morgello, S, Simpson, DM, McCutchan, JA, Barnholtz-Sloan, JS, Franklin, D, Rosario, D, Letendre, S, Grant, I, Kallianpur, AR
Corporate AuthorsCHARTER Group
JournalAm J Med Genet B Neuropsychiatr Genet
Volume174
Issue4
Pagination413-426
Date Published2017 Jun
ISSN1552-485X
KeywordsAdult, AIDS Dementia Complex, Biomarkers, CHARTER, Female, Follow-Up Studies, Genome-Wide Association Study, Genotype, Humans, Internal, Male, Middle Aged, neurocognitive disorders, Neuropsychological Tests, Polymorphism, Single Nucleotide, Prognosis, Prospective Studies
Abstract

HIV-associated neurocognitive disorder (HAND) often complicates HIV infection despite combination antiretroviral therapy (ART) and may be influenced by host genomics. We performed a genome-wide association study (GWAS) of HAND in 1,050 CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) Study participants. All participants underwent standardized, comprehensive neurocognitive, and neuromedical assessments to determine if they had cognitive impairment as assessed by the Global Deficit Score (GDS), and individuals with comorbidities that could confound diagnosis of HAND were excluded. Neurocognitive outcomes included GDS-defined neurocognitive impairment (NCI; binary GDS, 366 cases with GDS ≥ 0.5 and 684 controls with GDS < 0.5, and GDS as a continuous variable) and Frascati HAND definitions that incorporate assessment of functional impairment by self-report and performance-based criteria. Genotype data were obtained using the Affymetrix Human SNP Array 6.0 platform. Multivariable logistic or linear regression-based association tests were performed for GDS-defined NCI and HAND. GWAS results did not reveal SNPs meeting the genome-wide significance threshold (5.0 × 10 ) for GDS-defined NCI or HAND. For binary GDS, the most significant SNPs were rs6542826 (P = 8.1 × 10 ) and rs11681615 (1.2 × 10 ), both located on chromosome 2 in SH3RF3. The most significant SNP for continuous GDS was rs11157436 (P = 1.3 × 10 ) on chromosome 14 in the T-cell-receptor alpha locus; three other SNPs in this gene were also associated with binary GDS (P ≤ 2.9 × 10 ). This GWAS, conducted among ART-era participants from a single cohort with robust neurological phenotyping, suggests roles for several biologically plausible loci in HAND that deserve further exploration. © 2017 Wiley Periodicals, Inc.

DOI10.1002/ajmg.b.32530
Alternate JournalAm. J. Med. Genet. B Neuropsychiatr. Genet.
PubMed ID28447399
PubMed Central IDPMC5435520
Grant ListHHSN271201000030C / MH / NIMH NIH HHS / United States
HHSN271201000036C / MH / NIMH NIH HHS / United States
HHSN271201000027C / MH / NIMH NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
R01 LM011177 / LM / NLM NIH HHS / United States
N01 MH022005 / MH / NIMH NIH HHS / United States
R01 MH107345 / MH / NIMH NIH HHS / United States
R01 MH095621 / MH / NIMH NIH HHS / United States
U24 MH100930 / MH / NIMH NIH HHS / United States