SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Allison Matthew) "

Sökning: WFRF:(Allison Matthew)

  • Resultat 1-10 av 33
  • [1]234Nästa
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Fresard, Laure, et al. (författare)
  • Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
  • 2019
  • Ingår i: Nature Medicine. - NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.</p>
  •  
2.
  • Chu, Audrey Y, et al. (författare)
  • Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation
  • 2017
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 49:1, s. 125-130
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Variation in body fat distribution contributes to the metabolic sequelae of obesity. The genetic determinants of body fat distribution are poorly understood. The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size-weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men of European, African, Hispanic and Chinese ancestry, with and without sex stratification, for six traits associated with ectopic fat (hereinafter referred to as ectopic-fat traits). In total, we identified seven new loci associated with ectopic-fat traits (ATXN1, UBE2E2, EBF1, RREB1, GSDMB, GRAMD3 and ENSA; P &lt; 5 × 10(-8); false discovery rate &lt; 1%). Functional analysis of these genes showed that loss of function of either Atxn1 or Ube2e2 in primary mouse adipose progenitor cells impaired adipocyte differentiation, suggesting physiological roles for ATXN1 and UBE2E2 in adipogenesis. Future studies are necessary to further explore the mechanisms by which these genes affect adipocyte biology and how their perturbations contribute to systemic metabolic disease.</p>
  •  
3.
  • Joshi, Peter K, et al. (författare)
  • Directional dominance on stature and cognition in diverse human populations
  • 2015
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P &lt; 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.</p>
  •  
4.
5.
  • Nielson, Carrie M., et al. (författare)
  • Novel Genetic Variants Associated With Increased Vertebral Volumetric BMD, Reduced Vertebral Fracture Risk, and Increased Expression of SLC1A3 and EPHB2
  • 2016
  • Ingår i: Journal of Bone and Mineral Research. - AMBMR. - 0884-0431. ; 31:12, s. 2085-2097
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWASs) have revealed numerous loci for areal bone mineral density (aBMD). We completed the first GWAS meta-analysis (n=15,275) of lumbar spine volumetric BMD (vBMD) measured by quantitative computed tomography (QCT), allowing for examination of the trabecular bone compartment. SNPs that were significantly associated with vBMD were also examined in two GWAS meta-analyses to determine associations with morphometric vertebral fracture (n=21,701) and clinical vertebral fracture (n=5893). Expression quantitative trait locus (eQTL) analyses of iliac crest biopsies were performed in 84 postmenopausal women, and murine osteoblast expression of genes implicated by eQTL or by proximity to vBMD-associated SNPs was examined. We identified significant vBMD associations with five loci, including: 1p36.12, containing WNT4 and ZBTB40; 8q24, containing TNFRSF11B; and 13q14, containing AKAP11 and TNFSF11. Two loci (5p13 and 1p36.12) also contained associations with radiographic and clinical vertebral fracture, respectively. In 5p13, rs2468531 (minor allele frequency [MAF]=3%) was associated with higher vBMD (β=0.22, p=1.9×10-8) and decreased risk of radiographic vertebral fracture (odds ratio [OR]=0.75; false discovery rate [FDR] p=0.01). In 1p36.12, rs12742784 (MAF=21%) was associated with higher vBMD (β=0.09, p=1.2×10-10) and decreased risk of clinical vertebral fracture (OR=0.82; FDR p=7.4×10-4). Both SNPs are noncoding and were associated with increased mRNA expression levels in human bone biopsies: rs2468531 with SLC1A3 (β=0.28, FDR p=0.01, involved in glutamate signaling and osteogenic response to mechanical loading) and rs12742784 with EPHB2 (β=0.12, FDR p=1.7×10-3, functions in bone-related ephrin signaling). Both genes are expressed in murine osteoblasts. This is the first study to link SLC1A3 and EPHB2 to clinically relevant vertebral osteoporosis phenotypes. These results may help elucidate vertebral bone biology and novel approaches to reducing vertebral fracture incidence.
  •  
6.
  • Sodergren, Erica, et al. (författare)
  • The genome of the sea urchin Strongylocentrotus purpuratus
  • 2006
  • Ingår i: Science. - 0036-8075 .- 1095-9203. ; 314:5801, s. 941-952
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.</p>
  •  
7.
  • Thanassoulis, George, et al. (författare)
  • Genetic Associations with Valvular Calcification and Aortic Stenosis
  • 2013
  • Ingår i: New England Journal of Medicine. - Massachusetts Medical Society. - 0028-4793. ; 368:6, s. 503-512
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Limited information is available regarding genetic contributions to valvular calcification, which is an important precursor of clinical valve disease. Methods We determined genomewide associations with the presence of aortic-valve calcification (among 6942 participants) and mitral annular calcification (among 3795 participants), as detected by computed tomographic (CT) scanning; the study population for this analysis included persons of white European ancestry from three cohorts participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (discovery population). Findings were replicated in independent cohorts of persons with either CT-detected valvular calcification or clinical aortic stenosis. Results One SNP in the lipoprotein(a) (LPA) locus (rs10455872) reached genomewide significance for the presence of aortic-valve calcification (odds ratio per allele, 2.05; P = 9.0x10(-10)), a finding that was replicated in additional white European, African-American, and Hispanic-American cohorts (P<0.05 for all comparisons). Genetically determined Lp(a) levels, as predicted by LPA genotype, were also associated with aortic-valve calcification, supporting a causal role for Lp(a). In prospective analyses, LPA genotype was associated with incident aortic stenosis (hazard ratio per allele, 1.68; 95% confidence interval [CI], 1.32 to 2.15) and aortic-valve replacement (hazard ratio, 1.54; 95% CI, 1.05 to 2.27) in a large Swedish cohort; the association with incident aortic stenosis was also replicated in an independent Danish cohort. Two SNPs (rs17659543 and rs13415097) near the proinflammatory gene IL1F9 achieved genomewide significance for mitral annular calcification (P = 1.5x10(-8) and P = 1.8x10(-8), respectively), but the findings were not replicated consistently. Conclusions Genetic variation in the LPA locus, mediated by Lp(a) levels, is associated with aortic-valve calcification across multiple ethnic groups and with incident clinical aortic stenosis. (Funded by the National Heart, Lung, and Blood Institute and others.)
8.
  • Thorndyke, Michael C., 1946-, et al. (författare)
  • The genome of the sea urchin Strongylocentrotus purpuratus.
  • 2006
  • Ingår i: Science. - 1095-9203. ; 314:5801, s. 941-52
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
  •  
9.
  •  
10.
  • Allison, James, et al. (författare)
  • Analytical target cascading in aircraft design
  • 2006
  • Ingår i: 44th AIAA Aerospace Sciences Meeting and Exhibit : [Reno, Nevada, 9 - 12 January 2006]. - Reston, Va. : American Institute of Aeronautics and Astronautics, AIAA. - 1-563-47795-5 ; s. 16112-16120
  • Konferensbidrag (refereegranskat)abstract
    • <p>Analytical Target Cascading (ATC) is a product development tool that computes component design specifications such that the final system design is consistent and meets design targets. ATC is useful for complex product design that must be approached by decomposition, and facilitates concurrent design activities. While ATC has been applied successfully to automotive design, this article introduces the application of ATC to aircraft design, and discusses how it can be congruent with current design practice. ATC is used to solve an aircraft design problem where several flight regimes are considered separately. ATC can be used to balance low-fidelity system analysis and component-level multidisciplinary design optimization (MDO) activities. Finally, ATC may be used to coordinate overall aircraft design, with MDO employed to solve tightly coupled disciplinary problems that exist within ATC elements.</p>
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 33
  • [1]234Nästa
Åtkomst
fritt online (13)
Typ av publikation
tidskriftsartikel (31)
konferensbidrag (1)
forskningsöversikt (1)
Typ av innehåll
refereegranskat (33)
övrigt vetenskapligt (3)
Författare/redaktör
Guo, Xiuqing (13)
Lind, Lars, (10)
Allison, Matthew, (10)
Uitterlinden, Andre ... (10)
Ingelsson, Erik (10)
Morris, Andrew P. (10)
visa fler...
Harris, Tamara B. (10)
Trompet, Stella (9)
Ford, Ian (9)
Gudnason, Vilmundur (9)
Ikram, M. Arfan (9)
Mohlke, Karen L (9)
Scott, Robert A (9)
Feitosa, Mary F. (9)
Bergmann, Sven (9)
Liu, Yongmei (9)
Lu, Yingchang (9)
Mahajan, Anubha (9)
Yao, Jie (9)
Smith, Albert V. (8)
Teumer, Alexander (8)
Amouyel, Philippe (8)
Rotter, Jerome I. (8)
Van Duijn, Cornelia ... (8)
Ridker, Paul M., (8)
Chasman, Daniel I., (8)
Langenberg, Claudia (8)
Wood, Andrew R. (8)
Luan, Jian'an (8)
Perola, Markus (8)
Sattar, Naveed (8)
Bielak, Lawrence F. (8)
Franks, Paul W, (7)
Raitakari, Olli T (7)
Jukema, J. Wouter (7)
Deary, Ian J. (7)
Fornage, Myriam (7)
Wareham, Nicholas J (7)
Grarup, Niels, (7)
Pedersen, Oluf, (7)
Hansen, Torben, (7)
Salomaa, Veikko (7)
Gustafsson, Stefan (7)
Vedantam, Sailaja (7)
Winkler, Thomas W. (7)
Esko, Tonu (7)
Perry, John R. B. (7)
Balkau, Beverley (7)
Kardia, Sharon L R (7)
Nalls, Mike A. (7)
visa färre...
Lärosäte
Lunds universitet (11)
Umeå universitet (9)
Uppsala universitet (9)
Göteborgs universitet (4)
Luleå tekniska universitet (1)
Linköpings universitet (1)
visa fler...
Chalmers tekniska högskola (1)
visa färre...
Språk
Engelska (33)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (26)
Naturvetenskap (8)

År

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy