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- 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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- Morlighem, M., et al.
(författare)
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BedMachine v3 : Complete Bed Topography and Ocean Bathymetry Mapping of Greenland From Multibeam Echo Sounding Combined With Mass Conservation
- 2017
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 44:21, s. 11051-11061
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Tidskriftsartikel (refereegranskat)abstract
- Greenland's bed topography is a primary control on ice flow, grounding line migration, calving dynamics, and subglacial drainage. Moreover, fjord bathymetry regulates the penetration of warm Atlantic water (AW) that rapidly melts and undercuts Greenland's marine-terminating glaciers. Here we present a new compilation of Greenland bed topography that assimilates seafloor bathymetry and ice thickness data through a mass conservation approach. A new 150m horizontal resolution bed topography/bathymetric map of Greenland is constructed with seamless transitions at the ice/ocean interface, yielding major improvements over previous data sets, particularly in the marine-terminating sectors of northwest and southeast Greenland. Our map reveals that the total sea level potential of the Greenland ice sheet is 7.420.05m, which is 7cm greater than previous estimates. Furthermore, it explains recent calving front response of numerous outlet glaciers and reveals new pathways by which AW can access glaciers with marine-based basins, thereby highlighting sectors of Greenland that are most vulnerable to future oceanic forcing.
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- Munn-Chernoff, M. A., et al.
(författare)
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Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
- 2021
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Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r(g)], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from similar to 2400 to similar to 537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r(g) = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r(g) = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r(g) = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r(gs) = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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- Suri, P., et al.
(författare)
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Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain
- 2018
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Ingår i: PLoS Genet. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 14:9
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Tidskriftsartikel (refereegranskat)abstract
- Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). Adults of European ancestry were included from 15 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and from the UK Biobank interim data release. CBP cases were defined as those reporting back pain present for >= 3-6 months; non-cases were included as comparisons ("controls"). Each cohort conducted genotyping using commercially available arrays followed by imputation. GWAS used logistic regression models with additive genetic effects, adjusting for age, sex, study-specific covariates, and population substructure. The threshold for genome-wide significance in the fixed-effect inverse-variance weighted meta-analysis was p<5x10(-8). Suggestive (p<5x10(-7)) and genome-wide significant (p<5x10(-8)) variants were carried forward for replication or further investigation in the remaining UK Biobank participants not included in the discovery sample. The discovery sample comprised 158,025 individuals, including 29,531 CBP cases. A genome-wide significant association was found for the intronic variant rs12310519 in SOX5 (OR 1.08, p = 7.2x10(-10)). This was subsequently replicated in 283,752 UK Biobank participants not included in the discovery sample, including 50,915 cases (OR 1.06, p= 5.3x10(-11)), and exceeded genome-wide significance in joint meta-analysis (OR 1.07, p= 4.5x10(-19)). We found suggestive associations at three other loci in the discovery sample, two of which exceeded genome-wide significance in joint meta-analysis: an intergenic variant, rs7833174, located between CCDC26 and GSDMC (OR 1.05, p = 4.4x10(-13)), and an intronic variant, rs4384683, in DCC (OR 0.97, p = 2.4x10(-19)). In this first reported meta-analysis of GWAS for CBP, we identified and replicated a genetic locus associated with CBP (SOX5). We also identified 2 other loci that reached genome-wide significance in a 2-stage joint meta-analysis (CCDC26/GSDMC and DCC).
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