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We performed a genome\u2010wide association study (GWAS) of HAND in 1,050 CNS HIV Anti\u2010Retroviral 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\u2010defined neurocognitive impairment (NCI; binary GDS, 366 cases with GDS\u2009\u2265\u20090.5 and 684 controls with GDS\u2009&lt;\u20090.5, and GDS as a continuous variable) and Frascati HAND definitions that incorporate assessment of functional impairment by self\u2010report and performance\u2010based criteria. Genotype data were obtained using the Affymetrix Human SNP Array 6.0 platform. Multivariable logistic or linear regression\u2010based association tests were performed for GDS\u2010defined NCI and HAND. GWAS results did not reveal SNPs meeting the genome\u2010wide significance threshold (5.0\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>) for GDS\u2010defined NCI or HAND. For binary GDS, the most significant SNPs were rs6542826 (<jats:italic>P<\/jats:italic>\u2009=\u20098.1\u2009\u00d7\u200910<jats:sup>\u22127<\/jats:sup>) and rs11681615 (1.2\u2009\u00d7\u200910<jats:sup>\u22126<\/jats:sup>), both located on chromosome 2 in <jats:italic>SH3RF3<\/jats:italic>. The most significant SNP for continuous GDS was rs11157436 (<jats:italic>P<\/jats:italic>\u2009=\u20091.3\u2009\u00d7\u200910<jats:sup>\u22127<\/jats:sup>) on chromosome 14 in the T\u2010cell\u2010receptor <jats:italic>alpha<\/jats:italic> locus; three other SNPs in this gene were also associated with binary GDS (<jats:italic>P<\/jats:italic>\u2009\u2264\u20092.9\u2009\u00d7\u200910<jats:sup>\u22126<\/jats:sup>). This GWAS, conducted among ART\u2010era participants from a single cohort with robust neurological phenotyping, suggests roles for several biologically plausible loci in HAND that deserve further exploration. \u00a9 2017 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.b.32530","type":"journal-article","created":{"date-parts":[[2017,4,27]],"date-time":"2017-04-27T04:43:17Z","timestamp":1493268197000},"page":"413-426","source":"Crossref","is-referenced-by-count":32,"title":["Genome\u2010wide association study of HIV\u2010associated neurocognitive disorder (HAND): A CHARTER group study"],"prefix":"10.1002","volume":"174","author":[{"given":"Peilin","family":"Jia","sequence":"first","affiliation":[{"name":"Center for Precision Health, School of Biomedical Informatics The University of Texas Health Science Center at Houston Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongming","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Precision Health, School of Biomedical Informatics The University of Texas Health Science Center at Houston Houston Texas"},{"name":"Department of Biomedical Informatics Vanderbilt University Medical Center Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Hulgan","sequence":"additional","affiliation":[{"name":"Department of Medicine Vanderbilt University Medical Center Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William S.","family":"Bush","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, and Institute for Computational Biology Case Western Reserve University Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Samuels","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics Vanderbilt University School of Medicine Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinnamon S.","family":"Bloss","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of California San Diego San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert K.","family":"Heaton","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of California San Diego San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald J.","family":"Ellis","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California San Diego San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Schork","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of California San Diego San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina M.","family":"Marra","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann C.","family":"Collier","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Clifford","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin B.","family":"Gelman","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Texas Medical Branch Galveston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ned","family":"Sacktor","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Morgello","sequence":"additional","affiliation":[{"name":"Department of Neurology Icahn School of Medicine of Mount Sinai New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Department of Neurology Icahn School of Medicine of Mount Sinai New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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