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- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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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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| 2. |
- Liu, Ching-Ti, et al.
(författare)
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Assessment of gene-by-sex interaction effect on bone mineral density
- 2012
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 27:10, s. 2051-2064
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Tidskriftsartikel (refereegranskat)abstract
- Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p?
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| 3. |
- Krachler, Benno, 1966-, et al.
(författare)
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BMI and an anthropometry-based estimate of fat mass percentage are both valid discriminators of cardiometabolic risk : A comparison with DXA and bioimpedance
- 2013
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Ingår i: Journal of Obesity. - : Hindawi Publishing Corporation. - 2090-0708 .- 2090-0716. ; 2013
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine whether categories of obesity based on BMI and an anthropometry-based estimate of fat mass percentage (FM% equation) have similar discriminative ability for markers of cardiometabolic risk as measurements of FM% by dual-energy X-ray absorptiometry (DXA) or bioimpedance analysis (BIA).Design and Methods: A study of 40-79-year-old male (n = 205) and female (n = 388) Finns. Weight, height, blood pressure, triacylglycerols, HDL cholesterol, and fasting blood glucose were measured. Body composition was assessed by DXA and BIA and a FM%-equation.Results: For grade 1 hypertension, dyslipidaemia, and impaired fasting glucose >6.1 mmol/L, the categories of obesity as defined by BMI and the FM% equation had 1.9% to 3.7% (P < 0.01) higher discriminative power compared to DXA. For grade 2 hypertension the FM% equation discriminated 1.2% (P = 0.05) lower than DXA and 2.8% (P < 0.01) lower than BIA. Receiver operation characteristics confirmed BIA as best predictor of grade 2 hypertension and the FM% equation as best predictor of grade 1 hypertension. All other differences in area under curve were small (≤0.04) and 95% confidence intervals included 0.Conclusions: Both BMI and FM% equations may predict cardiometabolic risk with similar discriminative ability as FM% measured by DXA or BIA.
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