| 1. |
- 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. |
- Cheng, Sulin, et al.
(författare)
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Effects of calcium, dairy product, and vitamin D supplementation on bone mass accrual and body composition in 10-12-y-old girls: a 2-y randomized trial.
- 2005
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Ingår i: The American journal of clinical nutrition. - 0002-9165. ; 82:5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Little is known about the relative effectiveness of calcium supplementation from food or pills with or without vitamin D supplementation for bone mass accrual during the rapid growth period. OBJECTIVE: The purpose was to examine the effects of both food-based and pill supplements of calcium and vitamin D on bone mass and body composition in girls aged 10-12 y. DESIGN: This placebo-controlled intervention trial randomly assigned 195 healthy girls at Tanner stage I-II, aged 10-12 y, with dietary calcium intakes <900 mg/d to 1 of 4 groups: calcium (1000 mg) + vitamin D3 (200 IU), calcium (1000 mg), cheese (1000 mg calcium), and placebo. Primary outcomes were bone indexes of the hip, spine, and whole body by dual-energy X-ray absorptiometry and of the radius and tibia by peripheral quantitative computed tomography. RESULTS: With the use of intention-to-treat or efficacy analysis, calcium supplementation with cheese resulted in a higher percentage change in cortical thickness of the tibia than did placebo, calcium, or calcium + vitamin D treatment (P = 0.01, 0.038, and 0.004, respectively) and in higher whole-body bone mineral density than did placebo treatment (P = 0.044) when compliance was >50%. With the use of a hierarchical linear model with random effects to control for growth velocity, these differences disappeared. CONCLUSIONS: Increasing calcium intake by consuming cheese appears to be more beneficial for cortical bone mass accrual than the consumption of tablets containing a similar amount of calcium. Diverse patterns of growth velocity may mask the efficacy of supplementation in a short-term trial of children transiting through puberty.
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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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| 4. |
- 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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