| 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. |
- Karasik, D., et al.
(författare)
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Disentangling the genetics of lean mass
- 2019
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 109:2, s. 276-287
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age(2), and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LMwere termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection. Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.
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| 3. |
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| 4. |
- Cawthon, P. M., et al.
(författare)
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Putative Cut-Points in Sarcopenia Components and Incident Adverse Health Outcomes: AnSDOCAnalysis
- 2020
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Ingår i: Journal of the American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 68:7, s. 1429-1437
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES Analyses performed by the Sarcopenia Definitions and Outcomes Consortium (SDOC) identified cut-points in several metrics of grip strength for consideration in a definition of sarcopenia. We describe the associations between the SDOC-identified metrics of low grip strength (absolute or standardized to body size/composition); low dual-energy x-ray absorptiometry (DXA) lean mass as previously defined in the literature (appendicular lean mass [ALM]/ht(2)); and slowness (walking speed <.8 m/s) with subsequent adverse outcomes (falls, hip fractures, mobility limitation, and mortality). DESIGN Individual-level, sex-stratified pooled analysis. We calculated odds ratios (ORs) or hazard ratios (HRs) for incident falls, mobility limitation, hip fractures, and mortality. Follow-up time ranged from 1 year for falls to 8.8 +/- 2.3 years for mortality. SETTING Eight prospective observational cohort studies. PARTICIPANTS A total of 13,421 community-dwelling men and 4,828 community-dwelling women. MEASUREMENTS Grip strength by hand dynamometry, gait speed, and lean mass by DXA. RESULTS Low grip strength (absolute or standardized to body size/composition) was associated with incident outcomes, usually independently of slowness, in both men and women. ORs and HRs generally ranged from 1.2 to 3.0 for those below vs above the cut-point. DXA lean mass was not consistently associated with these outcomes. When considered together, those who had both muscle weakness by absolute grip strength (<35.5 kg in men and <20 kg in women) and slowness were consistently more likely to have a fall, hip fracture, mobility limitation, or die than those without either slowness or muscle weakness. CONCLUSION Older men and women with both muscle weakness and slowness have a higher likelihood of adverse health outcomes. These results support the inclusion of grip strength and walking speed as components in a summary definition of sarcopenia.
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| 5. |
- Manini, T. M., et al.
(författare)
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Identification of Sarcopenia Components That Discriminate Slow Walking Speed: A Pooled Data Analysis
- 2020
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Ingår i: Journal of the American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 68:7, s. 1419-1428
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The Sarcopenia Definitions and Outcomes Consortium (SDOC) sought to identify cut points for muscle strength and body composition measures derived from dual-energy x-ray absorptiometry (DXA) that discriminate older adults with slow walking speed. This article presents the core analyses used to guide the SDOC position statements. DESIGN Cross-sectional data analyses of pooled data. SETTING University-based research assessment centers. PARTICIPANTS Community-dwelling men (n = 13,652) and women: (n = 5,115) with information on lean mass by DXA, grip strength (GR), and walking speed. MEASUREMENTS Thirty-five candidate sarcopenia variables were entered into sex-stratified classification and regression tree (CART) models to agnostically choose variables and cut points that discriminate slow walkers (<0.80 m/s). Models with alternative walking speed outcomes were also evaluated (<0.60 and <1.0 m/s and walking speed treated continuously). RESULTS CART models identified GR/body mass index (GRBMI) and GR/total body fat (GRTBF) as the primary discriminating variables for slowness in men and women, respectively. Men with GRBMI of 1.05 kg/kg/m(2)or less were approximately four times more likely to be slow walkers than those with GRBMI of greater than 1.05 kg/kg/m(2). Women with GRTBF of less than 0.65 kg/kg were twice as likely to be slow walkers than women with GRTBF of 0.65 kg/kg or greater. Models with alternative walking speed outcomes selected only functions of GR as primary discriminators of slowness in both men and women. DXA-derived lean mass measures did not consistently discriminate slow walkers. CONCLUSION GR with and without adjustments for body size and composition consistently discriminated older adults with slowness. CART models did not select DXA-based lean mass as a primary discriminator of slowness. These results were presented to an SDOC Consensus Panel, who used them and other information to develop the SDOC Position Statements.
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| 6. |
- Yeap, B. B., et al.
(författare)
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Androgens in men study (AIMS): Protocol for meta-analyses of individual participant data investigating associations of androgens with health outcomes in men
- 2020
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Introduction This study aims to clarify the role(s) of endogenous sex hormones to influence health outcomes in men, specifically to define the associations of plasma testosterone with incidence of cardiovascular events, cancer, dementia and mortality risk, and to identify factors predicting testosterone concentrations. Data will be accrued from at least three Australian, two European and four North American population-based cohorts involving approximately 20 000 men. Methods and analysis Eligible studies include prospective cohort studies with baseline testosterone concentrations measured using mass spectrometry and 5 years of follow-up data on incident cardiovascular events, mortality, cancer diagnoses or deaths, new-onset dementia or decline in cognitive function recorded. Data for men, who were not taking androgens or drugs suppressing testosterone production, metabolism or action; and had no prior orchidectomy, are eligible. Systematic literature searches were conducted from 14 June 2019 to 31 December 2019, with no date range set for searches. Aggregate level data will be sought where individual participant data (IPD) are not available. One-stage IPD random-effects meta-analyses will be performed, using linear mixed models, generalised linear mixed models and either stratified or frailty-augmented Cox regression models. Heterogeneity in estimates from different studies will be quantified and bias investigated using funnel plots. Effect size estimates will be presented in forest plots and non-negligible heterogeneity and bias investigated using subgroup or meta-regression analyses. Ethics and dissemination Ethics approvals obtained for each of the participating cohorts state that participants have consented to have their data collected and used for research purposes. The Androgens In Men Study has been assessed as exempt from ethics review by the Human Ethics office at the University of Western Australia (file reference number RA/4/20/5014). Each of the component studies had obtained ethics approvals; please refer to respective component studies for details. Research findings will be disseminated to the scientific and broader community via the publication of four research articles, with each involving a separate set of IPD meta-analyses (articles will investigate different, distinct outcomes), at scientific conferences and meetings of relevant professional societies. Collaborating cohort studies will disseminate findings to study participants and local communities. PROSPERO registration number CRD42019139668. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.
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| 7. |
- Cawthon, Peggy M., et al.
(författare)
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Defining terms commonly used in sarcopenia research : a glossary proposed by the Global Leadership in Sarcopenia (GLIS) Steering Committee
- 2022
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Ingår i: European Geriatric Medicine. - : Springer. - 1878-7649 .- 1878-7657. ; 13:6, s. 1239-1244
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Tidskriftsartikel (refereegranskat)abstract
- MethodsThe aim of this paper is to define terms commonly related to sarcopenia to enable standardization of these terms in research and clinical settings. The Global Leadership Initiative in Sarcopenia (GLIS) aims to bring together leading investigators in sarcopenia research to develop a single definition that can be utilized worldwide; work on a global definition of sarcopenia is ongoing. The first step of GLIS is to develop the common terminology, or a glossary, that will facilitate agreement on a global definition of sarcopenia as well as interpretation of clinical and research findings.ResultsSeveral terms that are commonly used in sarcopenia research are defined, including self-reported measures of function and ability; objective physical performance tests; and measures related to muscle function and size.ConclusionAs new methods and technologies are developed, these definitions may be expanded or refined over time. Our goal is to promote this common language to describe sarcopenia and its components in clinical and research settings in order to increase clinical awareness and research interest in this important condition. We hope that the use of common terminology in sarcopenia research will increase understanding of the concept and improve communication around this important age-related condition.Key summary pointsAimThe aim of this paper is to define terms commonly related to sarcopenia to enable standardization of these terms in research and clinical settings.FindingsThis paper provides definitions for commonly used terminology in sarcopenia in both clinical and research settings. As new methods and technologies are developed, this terminology may be expanded or refined over time.MessageWe hope that the use of common terminology in sarcopenia research will increase understanding of the concept and improve communication around this important age-related condition.
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| 8. |
- Cawthon, Peggy M, et al.
(författare)
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What Cut-Point in Gait Speed Best Discriminates Community-Dwelling Older Adults With Mobility Complaints From Those Without? A Pooled Analysis From the Sarcopenia Definitions and Outcomes Consortium.
- 2021
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1758-535X .- 1079-5006. ; 76:10
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Tidskriftsartikel (refereegranskat)abstract
- Cut-points to define slow walking speed have largely been derived from expert opinion.Study participants (13 589 men and 5043 women aged ≥65years) had walking speed (m/s) measured over 4-6 m (mean ± SD: 1.20 ± 0.27 m/s in men and 0.94 ± 0.24 m/s in women.) Mobility limitation was defined as any self-reported difficulty with walking approximately 1/4 mile (prevalence: 12.6% men, 26.4% women). Sex-stratified classification and regression tree (CART) models with 10-fold cross-validation identified walking speed cut-points that optimally discriminated those who reported mobility limitation from those who did not.Among 5043 women, CART analysis identified 2 cut-points, classifying 4144 (82.2%) with walking speed ≥0.75 m/s, which we labeled as "fast"; 478 (9.5%) as "intermediate" (walking speed ≥0.62 m/s but <0.75 m/s); and 421 (8.3%) as "slow" (walking speed <0.62 m/s). Among 13 589 men, CART analysis identified 3 cut-points, classifying 10 001 (73.6%) with walking speed ≥1.00 m/s ("very fast"); 2901 (21.3%) as "fast" (walking speed ≥0.74 m/s but <1.00 m/s); 497 (3.7%) as "intermediate" (walking speed ≥0.57 m/s but <0.74 m/s); and 190 (1.4%) as "slow" (walking speed <0.57 m/s). Prevalence of self-reported mobility limitation was lowest in the "fast" or "very fast" (11% for men and 19% for women) and highest in the "slow" (60.5% in men and 71.0% in women). Rounding the 2 slower cut-points to 0.60 m/s and 0.75 m/s reclassified very few participants.Cut-points in walking speed of approximately 0.60 m/s and 0.75 m/s discriminate those with self-reported mobility limitation from those without.
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| 9. |
- Harvey, N. C., et al.
(författare)
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Greater pQCT Calf Muscle Density Is Associated with Lower Fracture Risk, Independent of FRAX, Falls and BMD: A Meta-Analysis in the Osteoporotic Fractures in Men (MrOS) Study
- 2022
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Ingår i: JBMR Plus. - : Wiley. - 2473-4039. ; 6:12
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the predictive performance of peripheral quantitative computed tomography (pQCT) measures of both calf muscle density (an established surrogate for muscle adiposity, with higher values indicating lower muscle adiposity and higher muscle quality) and size (cross-sectional area [CSA]) for incident fracture. pQCT (Stratec XCT2000/3000) measurements at the tibia were undertaken in Osteoporotic Fractures in Men (MrOS) United States (US), Hong Kong (HK), and Swedish (SW) cohorts. Analyses were by cohort and synthesized by meta-analysis. The predictive value for incident fracture outcomes, illustrated here for hip fracture (HF), using an extension of Poisson regression adjusted for age and follow-up time, was expressed as hazard ratio (HR) per standard deviation (SD) increase in exposure (HR/SD). Further analyses adjusted for femoral neck (fn) bone mineral density (BMD) T-score, Fracture Risk Assessment Tool (FRAX) 10-year fracture probability (major osteoporotic fracture) and prior falls. We studied 991 (US), 1662 (HK), and 1521 (SW) men, mean +/- SD age 77.0 +/- 5.1, 73.9 +/- 4.9, 80 +/- 3.4 years, followed for a mean +/- SD 7.8 +/- 2.2, 8.1 +/- 2.3, 5.3 +/- 2.0 years, with 31, 47, and 78 incident HFs, respectively. Both greater muscle CSA and greater muscle density were associated with a lower risk of incident HF [HR/SD: 0.84; 95% confidence interval [CI], 0.72-1.0 and 0.78; 95% CI, 0.66-0.91, respectively]. The pattern of associations was not materially changed by adjustment for prior falls or FRAX probability. In contrast, after inclusion of fn BMD T-score, the association for muscle CSA was no longer apparent (1.04; 95% CI, 0.88-1.24), whereas that for muscle density was not materially changed (0.69; 95% CI, 0.59-0.82). Findings were similar for osteoporotic fractures. pQCT measures of greater calf muscle density and CSA were both associated with lower incidence of fractures in older men, but only muscle density remained an independent risk factor for fracture after accounting for fn BMD. These findings demonstrate a complex interplay between measures of bone, muscle size, and quality, in determining fracture risk. (C) 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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