TY - JOUR
T1 - Association of a Polygenic Risk Score with Osteoporosis in People Living with HIV
T2 - The Swiss HIV Cohort Study
AU - Schwenke, Johannes M
AU - Thorball, Christian W
AU - Schoepf, Isabella C
AU - Ryom, Lene
AU - Hasse, Barbara
AU - Lamy, Olivier
AU - Calmy, Alexandra
AU - Wandeler, Gilles
AU - Marzolini, Catia
AU - Kahlert, Christian R
AU - Bernasconi, Enos
AU - Kouyos, Roger
AU - Günthard, Huldrych F
AU - Ledergerber, Bruno
AU - Fellay, Jacques
AU - Burkhalter, Felix
AU - Tarr, Philip E
AU - Swiss HIV Cohort Study
N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: [email protected].
PY - 2023/9/15
Y1 - 2023/9/15
N2 - 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.
AB - 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.
KW - Bone Density/genetics
KW - Bone Diseases, Metabolic/chemically induced
KW - Cohort Studies
KW - Female
KW - HIV
KW - HIV Infections/complications
KW - Humans
KW - Male
KW - Middle Aged
KW - Osteoporosis/epidemiology
KW - Risk Factors
KW - Switzerland/epidemiology
KW - Tenofovir/adverse effects
KW - osteoporosis
KW - aging
KW - low bone mineral density
KW - HIV infection
KW - polygenic risk score
UR - http://www.scopus.com/inward/record.url?scp=85173444253&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiad179
DO - 10.1093/infdis/jiad179
M3 - Journal article
C2 - 37225667
SN - 0022-1899
VL - 228
SP - 742
EP - 750
JO - The Journal of infectious diseases
JF - The Journal of infectious diseases
IS - 6
ER -