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- 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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| 2. |
- Korth, J., et al.
(författare)
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K2-140b and K2-180b - Characterization of a hot Jupiter and a mini-Neptune from the K2 mission
- 2019
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 482:2, s. 1807-1823
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Tidskriftsartikel (refereegranskat)abstract
- We report the independent discovery and characterization of two K2 planets: K2-180b, a mini-Neptune-sized planet in an 8.9-d orbit transiting a V = 12.6 mag, metal-poor ([Fe/H] = -0.65 ± 0.10) K2V star in K2 campaign 5; K2-140b, a transiting hot Jupiter in a 6.6-d orbit around a V = 12.6 mag G6V ([Fe/H] = + 0.10 ± 0.10) star in K2 campaign 10. Our results are based on K2 time-series photometry combined with high-spatial resolution imaging and high-precision radial velocity measurements. We present the first mass measurement of K2-180b. K2-180b has a mass of Mp = 11.3 ± 1.9 M_Earth and a radius of Rp = 2.2 ± 0.1 R_Earth, yielding a mean density of ρp = 5.6 ± 1.9 g cm-3, suggesting a rocky composition. Given its radius, K2-180b is above the region of the so-called `planetary radius gap'. K2-180b is in addition not only one of the densest mini-Neptune-sized planets, but also one of the few mini-Neptune-sized planets known to transit a metal-poor star. We also constrain the planetary and orbital parameters of K2-140b and show that, given the currently available Doppler measurements, the eccentricity is consistent with zero, contrary to the results of a previous study.
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| 3. |
- Hsu, Y. H., et al.
(författare)
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Meta-Analysis of Genomewide Association Studies Reveals Genetic Variants for Hip Bone Geometry
- 2019
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 34:7, s. 1284-1296
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Tidskriftsartikel (refereegranskat)abstract
- Hip geometry is an important predictor of fracture. We performed a meta-analysis of GWAS studies in adults to identify genetic variants that are associated with proximal femur geometry phenotypes. We analyzed four phenotypes: (i) femoral neck length; (ii) neck-shaft angle; (iii) femoral neck width, and (iv) femoral neck section modulus, estimated from DXA scans using algorithms of hip structure analysis. In the Discovery stage, 10 cohort studies were included in the fixed-effect meta-analysis, with up to 18,719 men and women ages 16 to 93 years. Association analyses were performed with similar to 2.5 million polymorphisms under an additive model adjusted for age, body mass index, and height. Replication analyses of meta-GWAS significant loci (at adjusted genomewide significance [GWS], threshold p <= 2.6 x 10(-8)) were performed in seven additional cohorts in silico. We looked up SNPs associated in our analysis, for association with height, bone mineral density (BMD), and fracture. In meta-analysis (combined Discovery and Replication stages), GWS associations were found at 5p15 (IRX1 and ADAMTS16); 5q35 near FGFR4; at 12p11 (in CCDC91); 11q13 (near LRP5 and PPP6R3 (rs7102273)). Several hip geometry signals overlapped with BMD, including LRP5 (chr. 11). Chr. 11 SNP rs7102273 was associated with any-type fracture (p = 7.5 x 10(-5)). We used bone transcriptome data and discovered several significant eQTLs, including rs7102273 and PPP6R3 expression (p = 0.0007), and rs6556301 (intergenic, chr.5 near FGFR4) and PDLIM7 expression (p = 0.005). In conclusion, we found associations between several genes and hip geometry measures that explained 12% to 22% of heritability at different sites. The results provide a defined set of genes related to biological pathways relevant to BMD and etiology of bone fragility. (c) 2019 American Society for Bone and Mineral Research.
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| 4. |
- Trevisan, Caterina, et al.
(författare)
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Nutritional Status, Body Mass Index, and the Risk of Falls in Community-Dwelling Older Adults : A Systematic Review and Meta-Analysis
- 2019
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Ingår i: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610 .- 1538-9375. ; 20:5, s. 569-582
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Forskningsöversikt (refereegranskat)abstract
- Objectives: To evaluate the association between nutritional status, defined on the basis of a multidimensional evaluation, and body mass index (BMI) with the risk of falls and recurrent falls in communitydwelling older people.Design: Systematic literature review and meta-analysis.Setting and Participants: Community-dwelling older adults.Measures: A systematic literature review was conducted on prospective studies identified through electronic and hand searches until October 2017. A random effects meta-analysis was used to evaluate the relative risk (RR) of experiencing falls and recurrent falls (>= 2 falls within at least 6 months) on the basis of nutritional status, defined by multidimensional scores. A random effects dose-response metaanalysis was used to evaluate the association between BMI and the risk of falls and recurrent falls.Results: People who were malnourished or those at risk for malnutrition had a pooled 45% higher risk of experiencing at least 1 fall than were those well-nourished (9510 subjects). Increased falls risk was observed in subjects malnourished versus well-nourished [RR 1.64, 95% confidence interval (CI) 1.182.28; 3 studies, 8379 subjects], whereas no substantial results were observed for risk of recurrent falls. A U-shaped association was detected between BMI and the risk for falls (P <. 001), with the nadir between 24.5 and 30 (144,934 subjects). Taking a BMI of 23.5 as reference, the pooled RR of falling ranged between 1.09 (95% CI 1.04-1.15) for a BMI of 17, to 1.07 (95% CI 0.92-1.24) for a BMI of 37.5. No associations were observed between BMI and recurrent falls (120,185 subjects).Conclusions/Implications: The results of our work suggest therefore that nutritional status and BMI should be evaluated when assessing the risk for falls in older age.
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