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Abstract
Background. The impact of human genetic background on low-trauma fracture (LTF) risk has not been evaluated in the context of human immunodeficiency virus (HIV) and clinical LTF risk factors.
Methods. In the general population, 6 common single-nucleotide polymorphisms (SNPs) associate with LTF through genome-wide association study. Using genome-wide SNP arrays and imputation, we genotyped these SNPs in HIV-positive, white Swiss HIV Cohort Study participants. We included 103 individuals with a first, physician-validated LTF and 206 controls matched on gender, whose duration of observation and whose antiretroviral therapy start dates were similar using incidence density sampling. Analyses of nongenetic LTF risk factors were based on 158 cases and 788 controls.
Results. A genetic risk score built from the 6 LTF-associated SNPs did not associate with LTF risk, in both models including and not including parental hip fracture history. The contribution of clinical LTF risk factors was limited in our dataset.
Conclusions. Genetic LTF markers with a modest effect size in the general population do not improve fracture prediction in persons with HIV, in whom clinical LTF risk factors are prevalent in both cases and controls.
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Details
1 Swiss Institute of Bioinformatics, Ecole Polytechnique Fédérale de Lausanne
2 Institute of Microbiology, University Hospital Center, University of Lausanne
3 Department of Bone Diseases, Geneva University Hospitals and Faculty of Medicine
4 Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich
5 Division of Infectious Diseases, Kantonsspital St. Gallen
6 Division of Infectious Diseases, Kantonsspital Aarau, University of Basel
7 Division of Infectious Diseases, Ospedale Regionale, Lugano
8 Department of Infectious Diseases, Bern University Hospital, University of Bern
9 Swiss Institute of Bioinformatics, Ecole Polytechnique Fédérale de Lausanne; Division of Infectious Diseases, University Hospital, Lausanne
10 Infectious Diseases Service, Kantonsspital Baselland, University of Basel, Bruderholz, Switzerland