title: Contribution of Genetic Background and Clinical Risk Factors to Low-Trauma Fractures in Human Immunodeficiency Virus (HIV)-Positive Persons: The Swiss HIV Cohort Study.
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.
authors.affiliation: Swiss Institute of Bioinformatics, Ecole Polytechnique Fédérale de Lausanne .
authors.forename: Thomas
authors.initials: T
authors.lastname: Junier
authors.affiliation: Institute of Microbiology , University Hospital Center, University of Lausanne .
authors.forename: Margalida
authors.initials: M
authors.lastname: Rotger
authors.affiliation: Department of Bone Diseases , Geneva University Hospitals and Faculty of Medicine .
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Biver
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology , University Hospital Zurich, University of Zurich .
authors.forename: Bruno
authors.initials: B
authors.lastname: Ledergerber
authors.affiliation: Institute of Microbiology , University Hospital Center, University of Lausanne .
authors.forename: Catalina
authors.initials: C
authors.lastname: Barceló
authors.affiliation: Swiss Institute of Bioinformatics, Ecole Polytechnique Fédérale de Lausanne .
authors.forename: Istvan
authors.initials: I
authors.lastname: Bartha
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology , University Hospital Zurich, University of Zurich .
authors.forename: Helen
authors.initials: H
authors.lastname: Kovari
authors.affiliation: Division of Infectious Diseases , Kantonsspital St. Gallen .
authors.forename: Patrick
authors.initials: P
authors.lastname: Schmid
authors.affiliation: Division of Infectious Diseases , Kantonsspital Aarau, University of Basel .
authors.forename: Christoph
authors.initials: C
authors.lastname: Fux
authors.affiliation: Division of Infectious Diseases , Ospedale Regionale , Lugano .
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.affiliation: Department of Infectious Diseases , Bern University Hospital, University of Bern .
authors.forename: Claudia
authors.initials: C
authors.lastname: Brun Del Re
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology , University Hospital Zurich, University of Zurich .
authors.forename: Rainer
authors.initials: R
authors.lastname: Weber
authors.affiliation: Swiss Institute of Bioinformatics, Ecole Polytechnique Fédérale de Lausanne,; Division of Infectious Diseases, University Hospital, Lausanne.
authors.forename: Jacques
authors.initials: J
authors.lastname: Fellay
authors.affiliation: Infectious Diseases Service, Kantonsspital Baselland , University of Basel , Bruderholz , Switzerland.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Tarr
keywords: HIV infection; antiretroviral therapy; genetics; low-trauma fracture; osteoporosis