Association of a Polygenic Risk Score With Osteoporosis in People Living With HIV: The Swiss HIV Cohort Study
Author:
Schwenke Johannes M1, Thorball Christian W23, Schoepf Isabella C14, Ryom Lene56, Hasse Barbara7, Lamy Olivier8, Calmy Alexandra9, Wandeler Gilles4, Marzolini Catia10ORCID, Kahlert Christian R11, Bernasconi Enos12, Kouyos Roger D713, Günthard Huldrych F713ORCID, Ledergerber Bruno7, Fellay Jacques23, Burkhalter Felix14, Tarr Philip E1ORCID, Abela I, Aebi-Popp K, Anagnostopoulos A, Battegay M, Bernasconi E, Braun D L, Bucher H C, Calmy A, Cavassini M, Ciuffi A, Dollenmaier G, Egger M, Elzi L, Fehr J, Fellay J, Furrer H, Fux C A, Günthard H F, Hachfeld A, Haerry D, Hasse B, Hirsch H H, Hoffmann M, Hösli I, Huber M, Jackson-Perry D, Kahlert C R, Kaiser L, Keiser O, Klimkait T, Kouyos R D, Kovari H, Kusejko K, Labhardt N, Leuzinger K, Martinez de Tejada B, Marzolini C, Metzner K J, Müller N, Nemeth J, Nicca D, Notter J, Paioni P, Pantaleo G, Perreau M, Rauch A, Salazar-Vizcaya L, Schmid P, Speck R, Stöckle M, Tarr P, Trkola A, Wandeler G, Weisser M, Yerly S,
Affiliation:
1. University Department of Medicine and Infectious Diseases Service, Kantonsspital Baselland, University of Basel, Bruderholz 2. Precision Medicine Unit, Lausanne University Hospital, University of Lausanne 3. School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne 4. Department of Infectious Diseases, Bern University Hospital, University of Bern , Switzerland 5. CHIP, Centre of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen 6. Department of Infectious Diseases, Hvidovre University Hospital , Denmark 7. Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich 8. Bone Unit, Lausanne University Hospital, University of Lausanne 9. Division of Infectious Disease, Geneva University Hospital 10. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel 11. Division of Infectious Diseases, Kantonsspital St Gallen 12. Division of Infectious Diseases, Ospedale Regionale Lugano, University of Geneva and Università della Svizzera italiana, Lugano 13. Institute of Medical Virology, University of Zurich 14. University Department of Nephrology and Dialysis, Kantonsspital Baselland, University of Basel, Bruderholz , Switzerland
Abstract
Abstract
Background
Bone mineral density (BMD) loss may be accelerated in people with HIV (PLWH). It is unknown whether a polygenic risk score (PRS) is associated with low BMD in PLWH.
Methods
Swiss HIV Cohort Study participants of self-reported European descent underwent ≥2 per-protocol dual x-ray absorptiometry (DXA) measurements ≥2 years apart (2011–2020). Univariable and multivariable odds ratios (ORs) for DXA-defined osteoporosis were based on traditional and HIV-related risk factors and a genome-wide PRS built from 9413 single-nucleotide polymorphisms associated with low BMD in the general population. Controls were free from osteoporosis/osteopenia on all DXA measurements.
Results
We included 438 participants: 149 with osteoporosis and 289 controls (median age, 53 years; 82% male, 95% with suppressed HIV RNA). Participants with unfavorable osteoporosis PRS (top vs bottom quintile) had univariable and multivariable-adjusted osteoporosis ORs of 4.76 (95% CI, 2.34–9.67) and 4.13 (1.86–9.18), respectively. For comparison, hepatitis C seropositivity, 5-year tenofovir disoproxil fumarate exposure, and parent history of hip fracture yielded univariable osteoporosis ORs of 2.26 (1.37–3.74), 1.84 (1.40–2.43), and 1.54 (0.82–2.9).
Conclusions
In PLWH in Switzerland, osteoporosis was independently associated with a BMD-associated PRS after adjustment for established risk factors, including exposure to tenofovir disoproxil fumarate.
Funder
SHCS Swiss National Science Foundation SHCS Research Foundation 5 Swiss university hospitals
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Immunology and Allergy
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