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, B.

AU - Lamy, Olivier

AU - Calmy, Alexandra

AU - Wandeler, G.

AU - Marzolini, C.

AU - Kahlert, Christian R.

AU - Bernasconi, Enos

AU - Kouyos, R. D.

AU - Günthard, H. F.

AU - Ledergerber, Bruno

AU - Fellay, Jacques

AU - Burkhalter, Felix

AU - Tarr, P.

AU - Swiss HIV Cohort Study (SHCS)

N1 - Publisher Copyright: © 2023 The Author(s). Published by Oxford University Press on behalf of Infectious Diseases Society of America.

PY - 2023

Y1 - 2023

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 - aging

KW - HIV infection

KW - low bone mineral density

KW - osteoporosis

KW - polygenic risk score

U2 - 10.1093/infdis/jiad179

DO - 10.1093/infdis/jiad179

M3 - Journal article

C2 - 37225667

AN - SCOPUS:85173444253

VL - 228

SP - 742

EP - 750

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 6

ER -