Self-reported neurocognitive complaints in the Swiss HIV Cohort Study: a viral genome-wide association study
Author:
Zeeb Marius12ORCID, Pasin Chloé12ORCID, Cavassini Matthias3ORCID, Bieler-Aeschlimann Mélanie3, Frischknecht Paul1, Kusejko Katharina12ORCID, Fellay Jacques34, Blanquart François5, Metzner Karin J12, Neumann Kathrin1, Jörimann Lisa12, Tschumi Jasmin12, Bernasconi Enos67ORCID, Huber Michael2ORCID, Kovari Helen8ORCID, Leuzinger Karoline910, Notter Julia11, Perreau Matthieu12, Rauch Andri13ORCID, Ramette Alban14, Stöckle Marcel10, Yerly Sabine15, Günthard Huldrych F12, Kouyos Roger D12, , Abela Irene, Aebi-Popp Karoline, Anagnostopoulos Alexia, Battegay Manuel, Bernasconi Enos, Braun Dominique L, Bucher Heiner C, Calmy Alexandra, Cavassini Matthias, Ciuffi Angela, Dollenmaier Günther, Egger Matthias, Elzi Luigia, Fehr Jan, Fellay Jacques, Furrer Hansjakob, Fux Christoph A, Günthard Huldrych F, Hachfeld Anna, Haerry David, Hasse Barbara, Hirsch Hans H, Hoffmann Matthias, Hösli Irene, Huber Michael, Jackson-Perry David, Kahlert Christian R, Keiser Olivia, Klimkait Thomas, Kouyos Roger D, Kovari Helen, Kusejko Katharina, Labhardt Niklaus, Leuzinger Karoline, Martinez de Tejada Begona, Marzolini Catia, Metzner Karin J, Müller Nicolas, Nemeth Johannes, Nicca Dunja, Notter Julia, Paioni Paolo, Pantaleo Giuseppe, Perreau Matthieu, Rauch Andri, Salazar-Vizcaya Luisa, Schmid Patrick, Speck Roberto, Stöckle Marcel, Tarr Philip, Trkola Alexandra, Wandeler Gilles, Weisser Maja, Yerly Sabine
Affiliation:
1. Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich , 8091 Zurich , Switzerland 2. Institute of Medical Virology, University of Zurich , 8057 Zurich , Switzerland 3. Division of Infectious Diseases, Lausanne University Hospital and University of Lausanne , 1011 Lausanne , Switzerland 4. Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne , 1015 Lausanne , Switzerland 5. Centre interdisciplinaire de recherche en biologie, Collége de France , 75231 Paris , France 6. Division of Infectious Diseases, Ente Ospedaliero Cantonale , 6500 Lugano , Switzerland 7. Division of Infectious Diseases, University of Geneva and University of Southern Switzerland , 6900 Lugano , Switzerland 8. Center for Infectious Diseases, Klinik im Park , 8027 Zurich , Switzerland 9. Division Infection Diagnostics, Department Biomedicine, University of Basel , 4001 Basel Switzerland 10. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel , 4031 Basel , Switzerland 11. Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen , 9007 St. Gallen , Switzerland 12. Division of Immunology and Allergy, Lausanne University Hospital and University of Lausanne , 1011 Lausanne , Switzerland 13. Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern , 3010 Bern , Switzerland 14. Institute for Infectious Diseases and Multidisciplinary Center for Infectious Diseases, University of Bern , 3012 Bern , Switzerland 15. Laboratory of Virology and Division of Infectious Diseases, Geneva University Hospital, University of Geneva , 1205 Geneva , Switzerland
Abstract
Abstract
People with HIV may report neurocognitive complaints, with or without associated neurocognitive impairment, varying between individuals and populations. While the HIV genome could play a major role, large systematic viral genome-wide screens to date are lacking. The Swiss HIV Cohort Study biannually enquires neurocognitive complaints. We quantified broad-sense heritability estimates using partial ‘pol’ sequences from the Swiss HIV Cohort Study resistance database and performed a viral near full-length genome-wide association study for the longitudinal area under the curve of neurocognitive complaints. We performed all analysis (i) restricted to HIV Subtype B and (ii) including all HIV subtypes. From 8547 people with HIV with neurocognitive complaints, we obtained 6966 partial ‘pol’ sequences and 2334 near full-length HIV sequences. Broad-sense heritability estimates for presence of memory loss complaints ranged between 1% and 17% (Subtype B restricted 1–22%) and increased with the stringency of the phylogenetic distance thresholds. The genome-wide association study revealed one amino acid (Env L641E), after adjusting for multiple testing, positively associated with memory loss complaints (P = 4.3 * 10−6). Other identified mutations, while insignificant after adjusting for multiple testing, were reported in other smaller studies (Tat T64N, Env *291S). We present the first HIV genome-wide association study analysis of neurocognitive complaints and report a first estimate for the heritability of neurocognitive complaints through HIV. Moreover, we could identify one mutation significantly associated with the presence of memory loss complaints. Our findings indicate that neurocognitive complaints are polygenetic and highlight advantages of a whole genome approach for pathogenicity determination.
Funder
Swiss National Science Foundation Yvonne Jacob Foundation University of Zurich Clinical Research Priority Program for Viral Infectious Disease Zurich Primary HIV Infection Cohort Study Gilead Sciences
Publisher
Oxford University Press (OUP)
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