| 1. |
- Johannesdottir, Fjola, et al.
(författare)
-
Distribution of cortical bone in the femoral neck and hip fracture: A prospective case-control analysis of 143 incident hip fractures; the AGES-REYKJAVIK Study
- 2011
-
Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 48:6, s. 1268-1276
-
Tidskriftsartikel (refereegranskat)abstract
- In this prospective nested case-control study we analyzed the circumferential differences in estimated cortical thickness (Est CTh) of the mid femoral neck as a risk factor for osteoporotic hip fractures in elderly women and men. Segmental QCT analysis of the mid femoral neck was applied to assess cortical thickness in anatomical quadrants. The superior region of the femoral neck was a stronger predictor for hip fracture than the inferior region, particularly in men. There were significant gender differences in Est CTh measurements in the control group but not in the case group. In multivariable analysis for risk of femoral neck (FN) fracture, Est CTh in the supero-anterior (SA) quadrant was significant in both women and men, and remained a significant predictor after adjustment for FN areal BMD (aBMD, dimensions g/cm(2), DXA-like), (p = 0.05 and p<0.0001, respectively). In conclusion, Est CTh in the SA quadrant best discriminated cases (n = 143) from controls (n = 298), especially in men. Cortical thinning superiorly in the hip might be of importance in determining resistance to fracture. (C) 2011 Elsevier Inc. All rights reserved.
|
|
| 2. |
- Johannesdottir, Fjola, et al.
(författare)
-
Mid-Thigh Cortical Bone Structural Parameters, Muscle Mass and Strength, and Association with Lower Limb Fractures in Older Men and Women (AGES-Reykjavik Study)
- 2012
-
Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 90:5, s. 354-364
-
Tidskriftsartikel (refereegranskat)abstract
- In a cross-sectional study we investigated the relationship between muscle and bone parameters in the mid-thigh in older people using data from a single axial computed tomographic section through the mid-thigh. Additionally, we studied the association of these variables with incident low-trauma lower limb fractures. A total of 3,762 older individuals (1,838 men and 1,924 women), aged 66-96 years, participants in the AGES-Reykjavik study, were studied. The total cross-sectional muscular area and knee extensor strength declined with age similarly in both sexes. Muscle parameters correlated most strongly with cortical area and total shaft area (adjusted for age, height, and weight) but explained < 10 % of variability in those bone parameters. The increment in medullary area (MA) and buckling ratio (BR) with age was almost fourfold greater in women than men. The association between MA and muscle parameters was nonsignificant. During a median follow-up of 5.3 years, 113 women and 66 men sustained incident lower limb fractures. Small muscular area, low knee extensor strength, large MA, low cortical thickness, and high BR were significantly associated with fractures in both sexes. Our results show that bone and muscle loss proceed at different rates and with different gender patterns.
|
|
| 3. |
- Rianon, Nahid J., et al.
(författare)
-
Fracture Risk Assessment in Older Adults Using a Combination of Selected Quantitative Computed Tomography Bone Measures: A Subanalysis of the Age, Gene/Environment Susceptibility-Reykjavik Study
- 2014
-
Ingår i: Journal of Clinical Densitometry. - : Elsevier BV. - 1094-6950. ; 17:1, s. 25-31
-
Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) and geometric bone measures are individually associated with prevalent osteoporotic fractures. Whether an aggregate of these measures would better associate with fractures has not been examined. We examined relationships between self-reported fractures and selected bone measures acquired by quantitative computerized tomography (QCT), a composite bone score, and QCT-acquired dual-energy X-ray absorptiometry-like total femur BMD in 2110 men and 2682 women in the Age, Gene/Environment Susceptibility-Reykjavik Study. The combined bone score was generated by summing gender-specific Z-scores for 4 QCT measures: vertebral trabecular BMD, femur neck cortical thickness, femur neck trabecular BMD, and femur neck minimal cross-sectional area. Except for the latter measure, lower scores for QCT measures, singly and combined, showed positive (p < 0.05) associations with fractures. Results remained the same in stratified models for participants not taking bone-promoting medication. In women on bone-promoting medication, greater femur neck cortical thickness and trabecular BMD were significantly associated with fracture status. However, the association between fracture and combined bone score was not stronger than the associations between fracture and individual measures or total femur BMD. Thus, the selected measures did not all similarly associate with fracture status and did not appear to have an additive effect on fracture status.
|
|
| 4. |
- 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.
|
|
| 5. |
- Gaulton, Kyle J, et al.
(författare)
-
Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
-
Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
|
|
| 6. |
- Helgadottir, Anna, et al.
(författare)
-
The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm
- 2008
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 217-224
-
Tidskriftsartikel (refereegranskat)abstract
- Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD)(1-4) and type 2 diabetes (T2D)(5-7), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.
|
|
| 7. |
- Kilpeläinen, Tuomas O, et al.
(författare)
-
Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.
- 2011
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:8, s. 753-60
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.
|
|
| 8. |
- Larsson, Daniel, et al.
(författare)
-
On some almost quadratic algebras coming from twisted derivations
- 2006
-
Ingår i: Journal of Nonlinear Mathematical Physics. - 1402-9251 .- 1776-0852. ; 13, s. 76-86
-
Tidskriftsartikel (refereegranskat)abstract
- This paper explores the quasi-deformation scheme devised in [1, 3] as applied to the simple Lie algebra sl(2)(F) for specific choices of the involved parameters and underlying algebras. One of the main points of this method is that the quasi-deformed algebra comes endowed with a canonical twisted Jacobi identity. We show in the present article that when the quasi-deformation method is applied to sl(2)(F) one obtains multiparameter families of almost quadratic algebras, and by choosing parameters suitably, sl(2)(F) is quasi-deformed into three-dimensional and four-dimensional Lie algebras and algebras closely resembling Lie superalgebras and colour Lie algebras, this being in stark contrast to the classical deformation schemes where sl(2)(F) is rigid.
|
|
| 9. |
- Larsson, Daniel, et al.
(författare)
-
On some almost quadratic algebras coming from twisted derivations
- 2006
-
Ingår i: Journal of Nonlinear Mathematical Physics. - : Springer Science and Business Media LLC. - 1402-9251 .- 1776-0852. ; 13, s. 76-86
-
Tidskriftsartikel (refereegranskat)abstract
- This paper explores the quasi-deformation scheme devised in [1, 3] as applied to the simple Lie algebra sl(2)(F) for specific choices of the involved parameters and underlying algebras. One of the main points of this method is that the quasi-deformed algebra comes endowed with a canonical twisted Jacobi identity. We show in the present article that when the quasi-deformation method is applied to sl(2)(F) one obtains multiparameter families of almost quadratic algebras, and by choosing parameters suitably, sl(2)(F) is quasi-deformed into three-dimensional and four-dimensional Lie algebras and algebras closely resembling Lie superalgebras and colour Lie algebras, this being in stark contrast to the classical deformation schemes where sl(2)(F) is rigid.
|
|
| 10. |
- Larsson, Daniel, et al.
(författare)
-
Quasi-Lie deformations on the algebra F[t]/(tn)
- 2008
-
Ingår i: Journal of Generalized Lie Theory and Applications. - 1736-5279 .- 1736-4337. ; 2:3, s. 201-205
-
Tidskriftsartikel (refereegranskat)abstract
- This paper explores the quasi-deformation scheme devised by Hartwig, Larsson and Silvestrov as applied to the simple Lie algebra sl2(F). One of the main points of this method is that the quasi-deformed algebra comes endowed with a canonical twisted Jacobi identity. We show in the present article that when the quasi-deformation method is applied to sl2(F) via representations by twisted derivations on the algebra F[t]/(tN) one obtains interesting new multi-parameter families of almost quadratic algebras.
|
|
