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Sökning: WFRF:(Pols H)

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1.
  • Oei, L., et al. (författare)
  • Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus
  • 2014
  • Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 59, s. 20-27
  • Tidskriftsartikel (refereegranskat)abstract
    • Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fracture applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55 years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey-Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey-Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han-Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p<5 x 10(-8). In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p = 4.6 x 10(-8). However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% Cl: 0.98-1.14; p = 0.17), displaying high degree of heterogeneity (I-2= 57%; Q(het)p = 0.0006). Under Han-Eskin alternative random effects model the summary effect was significant (p = 0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures. (C) 2013 Elsevier Inc. All rights reserved.
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2.
  • Kerkhof, H. J. M., et al. (författare)
  • Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: the TREAT-OA consortium
  • 2011
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 19:3, s. 254-264
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To address the need for standardization of osteoarthritis (OA) phenotypes by examining the effect of heterogeneity among symptomatic (SOA) and radiographic osteoarthritis (ROA) phenotypes. Methods: Descriptions of OA phenotypes of the 28 studies involved in the TREAT-OA consortium were collected. We investigated whether different OA definitions result in different association results by creating various hip OA definitions in one large population based cohort (the Rotterdam Study I (RSI)) and testing those for association with gender, age and body mass index using one-way ANOVA. For ROA, we standardized the hip-, knee- and hand ROA definitions and calculated prevalence's of ROA before and after standardization in nine cohort studies. This procedure could only be performed in cohort studies and standardization of SOA definitions was not feasible at this moment. Results: In this consortium, all studies with SOA phenotypes (knee, hip and hand) used a different definition and/or assessment of OA status. For knee-, hip- and hand ROA five, four and seven different definitions were used, respectively. Different hip ROA definitions do lead to different association results. For example, we showed in the RSI that hip OA defined as "at least definite joint space narrowing (JSN) and one definite osteophyte" was not associated with gender (P=0.22), but defined as "at least one definite osteophyte" was significantly associated with gender (P=3 x 10(-9)). Therefore, a standardization process was undertaken for ROA definitions. Before standardization a wide range of ROA prevalence's was observed in the nine cohorts studied. After standardization the range in prevalence of knee- and hip ROA was small. Conclusion: Phenotype definitions influence the prevalence of OA and association with clinical variables. ROA phenotypes within the TREAT-OA consortium were standardized to reduce heterogeneity and improve power in future genetics studies. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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4.
  • Kanis, J A, et al. (författare)
  • A meta-analysis of previous fracture and subsequent fracture risk.
  • 2004
  • Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 35:2, s. 375-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous fracture is a well-documented risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex, and bone mineral density (BMD). We studied 15259 men and 44902 women from 11 cohorts comprising EVOS/EPOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES, Hiroshima, and two cohorts from Gothenburg. Cohorts were followed for a total of 250000 person-years. The effect of a prior history of fracture on the risk of any fracture, any osteoporotic fracture, and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex, and BMD. The results of the different studies were merged by using the weighted beta-coefficients. A previous fracture history was associated with a significantly increased risk of any fracture compared with individuals without a prior fracture (RR = 1.86; 95% CI = 1.75-1.98). The risk ratio was similar for the outcome of osteoporotic fracture or for hip fracture. There was no significant difference in risk ratio between men and women. Risk ratio (RR) was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any fracture (8%) and for hip fracture (22%). The risk ratio was stable with age except in the case of hip fracture outcome where the risk ratio decreased significantly with age. We conclude that previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.
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5.
  • Kanis, J A, et al. (författare)
  • Smoking and fracture risk: a meta-analysis.
  • 2005
  • Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 16:2, s. 155-62
  • Tidskriftsartikel (refereegranskat)abstract
    • Smoking is widely considered a risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex and bone mineral density (BMD). We studied 59,232 men and women (74% female) from ten prospective cohorts comprising EVOS/EPOS, DOES, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, Hiroshima and two cohorts from Gothenburg. Cohorts were followed for a total of 250,000 person-years. The effect of current or past smoking, on the risk of any fracture, any osteoporotic fracture and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex and BMD. The results of the different studies were merged using the weighted beta-coefficients. Current smoking was associated with a significantly increased risk of any fracture compared to non-smokers (RR=1.25; 95% Confidence Interval (CI)=1.15-1.36). Risk ratio (RR) was adjusted marginally downward when account was taken of BMD, but it remained significantly increased (RR=1.13). For an osteoporotic fracture, the risk was marginally higher (RR=1.29; 95% CI=1.13-1.28). The highest risk was observed for hip fracture (RR=1.84; 95% CI=1.52-2.22), but this was also somewhat lower after adjustment for BMD (RR=1.60; 95% CI=1.27-2.02). Risk ratios were significantly higher in men than in women for all fractures and for osteoporotic fractures, but not for hip fracture. Low BMD accounted for only 23% of the smoking-related risk of hip fracture. Adjustment for body mass index had a small downward effect on risk for all fracture outcomes. For osteoporotic fracture, the risk ratio increased with age, but decreased with age for hip fracture. A smoking history was associated with a significantly increased risk of fracture compared with individuals with no smoking history, but the risk ratios were lower than for current smoking. We conclude that a history of smoking results in fracture risk that is substantially greater than that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.
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6.
  • Oei, Ling, et al. (författare)
  • A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus
  • 2014
  • Ingår i: Journal of Medical Genetics. - : BMJ Publishing Group. - 0022-2593 .- 1468-6244. ; 51:2, s. 122-131
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk.AIM: To identify CNVs associated with osteoporotic bone fracture risk.METHOD: We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies.RESULTS: A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p=8.69×10(-5)). We performed an in silico meta-analysis in four studies with CNV microarray data and the association with fracture risk was replicated (OR 3.11, 95% CI 1.01 to 8.22; p=0.02). The prevalence of this deletion showed geographic diversity, being absent in additional samples from Australia, Canada, Poland, Iceland, Denmark, and Sweden, but present in the Netherlands (0.34%), Spain (0.33%), USA (0.23%), England (0.15%), Scotland (0.10%), and Ireland (0.06%), with insufficient evidence for association with fracture risk.CONCLUSIONS: These results suggest that deletions in the 6p25.1 locus may predispose to higher risk of fracture in a subset of populations of European origin; larger and geographically restricted studies will be needed to confirm this regional association. This is a first step towards the evaluation of the role of rare CNVs in osteoporosis.
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7.
  • Uitterlinden, André G, et al. (författare)
  • The association between common vitamin D receptor gene variations and osteoporosis : a participant-level meta-analysis
  • 2006
  • Ingår i: Annals of Internal Medicine. - 0003-4819. ; 145:4, s. 255-264
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Polymorphisms of the vitamin D receptor (VDR) gene have been implicated in the genetic regulation of bone mineral density (BMD). However, the clinical impact of these variants remains unclear.OBJECTIVE: To evaluate the relation between VDR polymorphisms, BMD, and fractures.DESIGN: Prospective multicenter large-scale association study.SETTING: The Genetic Markers for Osteoporosis consortium, involving 9 European research teams.PARTICIPANTS: 26,242 participants (18,405 women).MEASUREMENTS: Cdx2 promoter, FokI, BsmI, ApaI, and TaqI polymorphisms; BMD at the femoral neck and the lumbar spine by dual x-ray absorptiometry; and fractures.RESULTS: Comparisons of BMD at the lumbar spine and femoral neck showed nonsignificant differences less than 0.011 g/cm2 for any genotype with or without adjustments. A total of 6067 participants reported a history of fracture, and 2088 had vertebral fractures. For all VDR alleles, odds ratios for fractures were very close to 1.00 (range, 0.98 to 1.02) and collectively the 95% CIs ranged from 0.94 (lowest) to 1.07 (highest). For vertebral fractures, we observed a 9% (95% CI, 0% to 18%; P = 0.039) risk reduction for the Cdx2 A-allele (13% risk reduction in a dominant model).LIMITATIONS: The authors analyzed only selected VDR polymorphisms. Heterogeneity was detected in some analyses and may reflect some differences in collection of fracture data across cohorts. Not all fractures were related to osteoporosis.CONCLUSIONS: The FokI, BsmI, ApaI, and TaqI VDR polymorphisms are not associated with BMD or with fractures, but the Cdx2 polymorphism may be associated with risk for vertebral fractures.
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8.
  • Beishuizen, CRL, et al. (författare)
  • Integrating nurses' experiences with supporting behaviour change for cardiovascular prevention into a self-management internet platform in Finland and the Netherlands: a qualitative study
  • 2019
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 9:6, s. e023480-
  • Tidskriftsartikel (refereegranskat)abstract
    • Global ageing is linked to an increased burden of cardiovascular disease and dementia, which calls for better prevention strategies. Self-management and eHealth applications are regarded as promising strategies to support prevention. The aim of this study was to explore nurses’ best practices concerning behaviour change guidance for cardiovascular (CV) prevention in order to learn how to optimally integrate them into a coach-supported internet platform for CV self-management.DesignQualitative focus group study in Finland and the Netherlands. Discussions were audiotaped and transcribed. Data were thematically analysed following principles of grounded theory.SettingDutch and Finnish primary care settings.ParticipantsSix Finnish and seven Dutch primary care nurses with experience in CV prevention.ResultsSimilar best practices were found in both countries and comprised of (1) establishing a relationship of trust, (2) managing awareness and expectations and (3) appropriate timing and monitoring of the process of behaviour change. However, the Finnish and Dutch nurses used different approaches for accomplishment of these practices, which was reflected in their recommendations for online support. Both groups emphasised that online support should be combined with human support and integrated into regular care. Finnish nurses had more confidence in patient self-management and remote communication than Dutch nurses, who emphasised the importance of face-to-face contact and preferred to keep control of medical aspects of prevention.ConclusionsDifferences in Dutch and Finnish’s nurses’ practices for supporting CV prevention appear to reflect their local healthcare practices, which should be taken into account when designing internet platforms for health self-management. Including cognitive health as a goal of CV prevention might stimulate motivation for health behaviour change.Trial registration numberISRCTN48151589; Pre-results.
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9.
  • Estrada, Karol, et al. (författare)
  • Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
  • 2012
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
  • Tidskriftsartikel (refereegranskat)abstract
    • Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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10.
  • Kanis, J A, et al. (författare)
  • A family history of fracture and fracture risk: a meta-analysis.
  • 2004
  • Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 35:5, s. 1029-37
  • Tidskriftsartikel (refereegranskat)abstract
    • The aims of the present study were to determine whether a parental history of any fracture or hip fracture specifically are significant risk factors for future fracture in an international setting, and to explore the effects of age, sex and bone mineral density (BMD) on this risk. We studied 34,928 men and women from seven prospectively studied cohorts followed for 134,374 person-years. The cohorts comprised the EPOS/EVOS study, CaMos, the Rotterdam Study, DOES and cohorts at Sheffield, Rochester and Gothenburg. The effect of family history of osteoporotic fracture or of hip fracture in first-degree relatives, BMD and age on all clinical fracture, osteoporotic fracture and hip fracture risk alone was examined using Poisson regression in each cohort and for each sex. The results of the different studies were merged from the weighted beta coefficients. A parental history of fracture was associated with a modest but significantly increased risk of any fracture, osteoporotic fracture and hip fracture in men and women combined. The risk ratio (RR) for any fracture was 1.17 (95% CI=1.07-1.28), for any osteoporotic fracture was 1.18 (95% CI=1.06-1.31), and for hip fracture was 1.49 (95% CI=1.17-1.89). The risk ratio was higher at younger ages but not significantly so. No significant difference in risk was seen between men and women with a parental history for any fracture (RR=1.17 and 1.17, respectively) or for an osteoporotic fracture (RR=1.17 and 1.18, respectively). For hip fracture, the risk ratios were somewhat higher, but not significantly higher, in men than in women (RR=2.02 and 1.38, respectively). A family history of hip fracture in parents was associated with a significant risk both of all osteoporotic fracture (RR 1.54; 95CI=1.25-1.88) and of hip fracture (RR=2.27; 95% CI=1.47-3.49). The risk was not significantly changed when BMD was added to the model. We conclude that a parental history of fracture (particularly a family history of hip fracture) confers an increased risk of fracture that is independent of BMD. Its identification on an international basis supports the use of this risk factor in case-finding strategies.
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