| 1. |
- Zillikens, M. C., et al.
(författare)
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Large meta-analysis of genome-wide association studies identifies five loci for lean body mass
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 x 10(-8)) or suggestively genome wide (p < 2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.
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| 2. |
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| 3. |
- Zheng, Hou-Feng, et al.
(författare)
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Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112-
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Tidskriftsartikel (refereegranskat)abstract
- The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
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| 4. |
- Åkesson, Kristina E., et al.
(författare)
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Closing the Osteoporosis Care Gap
- 2021
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Ingår i: Current Osteoporosis Reports. - : Springer Science and Business Media LLC. - 1544-1873 .- 1544-2241. ; 19:1, s. 58-65
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Forskningsöversikt (refereegranskat)abstract
- Purpose of Review: This review outlines the scope of the problem in osteoporosis care and secondary fracture prevention and describes fracture prevention strategies, with a focus on the frail elderly. Recent Findings: Despite heightened awareness among patients and clinicians alike and the availability of efficacious anti-osteoporosis medications, osteoporosis is still underdiagnosed and undertreated. However, the introduction of systematic risk assessment and secondary fracture prevention programmes has gained momentum, and evidence of success is accumulating. Summary: We possess today the knowledge required to close the osteoporosis care gap. The basic components in a secondary prevention model are similar in all health care settings, number one being a dedicated fracture coordinator, with anti-osteoporosis medications and multifaceted falls prevention as cornerstones, particularly in the frailest, both in the near and long-term. Initiation of structured care pathways including the key elements – identification, investigation, intervention and follow-up of adherence – demonstrably reduces re-fracture rates and is cost-effective.
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| 5. |
- Sandström, Linnéa, et al.
(författare)
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Peak Bone Mass and Quantitative Ultrasound Bone Properties in Young Adulthood : A Study in the PEAK-25 Cohort of Women
- 2016
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Ingår i: Journal of Clinical Densitometry. - : Elsevier BV. - 1094-6950. ; 19:4, s. 477-484
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Tidskriftsartikel (refereegranskat)abstract
- Peak bone mass is normally reached in the third decade of life. Previously, in the population-based PEAK-25 cohort (n = 1061, age 25.5 ± 0.2), we demonstrated that bone mineral density in the population-based PEAK-25 cohort is comparatively high; therefore, this study aimed to determine if the calcaneus microarchitecture mirrored this. In the process, we describe normative quantitative ultrasound (QUS) values for 25-yr-old women and the relationship between QUS values and extremes of body weight. QUS variables speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index were measured. Young adult values were based on the manufacturer-supplied QUS reference values. Analyses were performed in the cohort as a whole, and additionally, to understand the relationship between body weight and QUS values in young women, the variables were categorized into octiles for weight or body mass index (BMI) and the lowest and highest octiles were compared. In the cohort, SOS values, reflecting bone density, were higher (108 ± 18%), whereas BUA values, reflecting bone complexity, were lower (90 ± 14%) compared to the young adult reference population. SOS did not correlate with body weight or BMI. In the cohort, overall correlations between BUA weight, and BMI were small and positive (Pearson's r coefficients 0.261 and 0.197, respectively; p <0.001), although in the low-weight group, r coefficients were higher (r = 0.313 and 0.268; p <0.05). In contrast, in the high-weight group, correlation with BUA values tended to be small, negative, and nonsignificant. Correlation between QUS and dual-energy X-ray absorptiometry-measured bone mineral density was low to moderate and significant at all skeletal sites (r = 0.37-0.52). Whereas coefficients tended to be higher in the low-weight group, the reverse was apparent for the low-BMI group. In these 25-yr-old women, a comparatively high dual-energy X-ray absorptiometry-measured bone mass is offset by less complex bone structures assessed by QUS. This may have implications for later osteoporosis assessment and future fracture risk.
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