Association of a Polygenic Risk Score with Osteoporosis in People Living with HIV: The Swiss HIV Cohort Study

Johannes M Schwenke*, Christian W Thorball, Isabella C Schoepf, Lene Ryom, Barbara Hasse, Olivier Lamy, Alexandra Calmy, Gilles Wandeler, Catia Marzolini, Christian R Kahlert, Enos Bernasconi, Roger Kouyos, Huldrych F Günthard, Bruno Ledergerber, Jacques Fellay, Felix Burkhalter, Philip E Tarr*, Swiss HIV Cohort Study

*Corresponding author af dette arbejde

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.

OriginalsprogEngelsk
TidsskriftThe Journal of infectious diseases
Vol/bind228
Udgave nummer6
Sider (fra-til)742-750
Antal sider9
ISSN0022-1899
DOI
StatusUdgivet - 15 sep. 2023

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