| Title: |
Genome‐wide association study of HIV‐associated neurocognitive disorder (HAND): A CHARTER group study |
| Authors: |
Jia, Peilin; Zhao, Zhongming; Hulgan, Todd; Bush, William S; Samuels, David C; Bloss, Cinnamon S; Heaton, Robert K; Ellis, Ronald J; Schork, Nicholas; Marra, Christina M; Collier, Ann C; Clifford, David B; Gelman, Benjamin B; Sacktor, Ned; Morgello, Susan; Simpson, David M; McCutchan, J Allen; Barnholtz‐Sloan, Jill S; Franklin, Donald R; Rosario, Debralee; Letendre, Scott L; Grant, Igor; Kallianpur, Asha R; Group, for the CHARTER Study |
| Source: |
American Journal of Medical Genetics Part B Neuropsychiatric Genetics, vol 174, iss 4 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2017 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
Biological Sciences; Biomedical and Clinical Sciences; Genetics; Human Genome; Basic Behavioral and Social Science; Acquired Cognitive Impairment; Neurosciences; Brain Disorders; Infectious Diseases; Neurodegenerative; HIV/AIDS; Clinical Research; Behavioral and Social Science; Sexually Transmitted Infections; Mental Health; 2.1 Biological and endogenous factors; Good Health and Well Being; AIDS Dementia Complex; Adult; Biomarkers; Female; Follow-Up Studies; Genome-Wide Association Study; Genotype; Humans; Male; Middle Aged; Neurocognitive Disorders; Neuropsychological Tests; Polymorphism |
| Subject Geographic: |
413 - 426 |
| Description: |
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 × 10-8 ) for GDS-defined NCI or HAND. For binary GDS, the most significant SNPs were rs6542826 (P = 8.1 × 10-7 ) and rs11681615 (1.2 × 10-6 ), both located on chromosome 2 in SH3RF3. The most significant SNP for continuous GDS was rs11157436 (P = 1.3 × 10-7 ) 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 × 10-6 ). 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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt3383r9r8; https://escholarship.org/uc/item/3383r9r8; https://escholarship.org/content/qt3383r9r8/qt3383r9r8.pdf |
| DOI: |
10.1002/ajmg.b.32530 |
| Availability: |
https://escholarship.org/uc/item/3383r9r8; https://escholarship.org/content/qt3383r9r8/qt3383r9r8.pdf; https://doi.org/10.1002/ajmg.b.32530 |
| Rights: |
public |
| Accession Number: |
edsbas.6110DFC6 |
| Database: |
BASE |