Dataset Information

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

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.

SUBMITTER: Schwenke JM

PROVIDER: S-EPMC10503954 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Schwenke Johannes M JM Thorball Christian W CW Schoepf Isabella C IC Ryom Lene L Hasse Barbara B Lamy Olivier O Calmy Alexandra A Wandeler Gilles G Marzolini Catia C Kahlert Christian R CR Bernasconi Enos E Kouyos Roger D RD Günthard Huldrych F HF Ledergerber Bruno B Fellay Jacques J Burkhalter Felix F Tarr Philip E PE

The Journal of infectious diseases 20230901 6

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 37225667

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Project description:ImportanceMyopia is a leading cause of untreatable visual impairment and is increasing in prevalence worldwide. Interventions for slowing childhood myopia progression have shown success in randomized clinical trials; hence, there is a need to identify which children would benefit most from treatment intervention.ObjectivesTo examine whether genetic information alone can identify children at risk of myopia development and whether including a child's genetic predisposition to educational attainment is associated with improved genetic prediction of the risk of myopia.Design, setting, and participantsMeta-analysis of 3 genome-wide association studies (GWAS) including a total of 711 984 individuals. These were a published GWAS for educational attainment and 2 GWAS for refractive error in the UK Biobank, which is a multisite cohort study that recruited participants between January 2006 and October 2010. A polygenic risk score was applied in a population-based validation sample examined between September 1998 and September 2000 (Avon Longitudinal Study of Parents and Children [ALSPAC] mothers). Data analysis was performed from February 2018 to May 2019.Main outcomes and measuresThe primary outcome was the area under the receiver operating characteristic curve (AUROC) in analyses for predicting myopia, using noncycloplegic autorefraction measurements for myopia severity levels of less than or equal to -0.75 diopter (D) (any), less than or equal to -3.00 D (moderate), or less than or equal to -5.00 D (high). The predictor variable was a polygenic risk score (PRS) derived from genome-wide association study data for refractive error (n = 95 619), age of onset of spectacle wear (n = 287 448), and educational attainment (n = 328 917).ResultsA total of 383 067 adults aged 40 to 69 years from the UK Biobank were included in the new GWAS analyses. The PRS was evaluated in 1516 adults aged 24 to 51 years from the ALSPAC mothers cohort. The PRS had an AUROC of 0.67 (95% CI, 0.65-0.70) for myopia, 0.75 (95% CI, 0.70-0.79) for moderate myopia, and 0.73 (95% CI, 0.66-0.80) for high myopia. Inclusion in the PRS of information associated with genetic predisposition to educational attainment marginally improved the AUROC for myopia (AUROC, 0.674 vs 0.668; P = .02), but not those for moderate and high myopia. Individuals with a PRS in the top 10% were at 6.1-fold higher risk (95% CI, 3.4-10.9) of high myopia.Conclusions and relevanceA personalized medicine approach may be feasible for detecting very young children at risk of myopia. However, accuracy must improve further to merit uptake in clinical practice; currently, cycloplegic autorefraction remains a better indicator of myopia risk (AUROC, 0.87).

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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