SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Heinz Judith) "

Sökning: WFRF:(Heinz Judith)

  • Resultat 1-10 av 18
  • [1]2Nästa
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Shungin, Dmitry, et al. (författare)
  • New genetic loci link adipose and insulin biology to body fat distribution
  • 2015
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-196
  • Tidskriftsartikel (refereegranskat)abstract
    • Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
  •  
2.
  • Bornholdt, Dorothea, et al. (författare)
  • Genotype-Phenotype Correlations Emerging from the Identification of Missense Mutations in MBTPS2
  • 2013
  • Ingår i: Human Mutation. - 1059-7794 .- 1098-1004. ; 34:4, s. 587-594
  • Tidskriftsartikel (refereegranskat)abstract
    • Missense mutations affecting membrane-bound transcription factor protease site 2 (MBTPS2) have been associated with Ichthyosis Follicularis with Atrichia and Photophobia (IFAP) syndrome with or without BRESHECK syndrome, with keratosis follicularis spinulosa decalvans, and Olmsted syndrome. This metalloprotease activates, by intramembranous trimming in conjunction with the protease MBTPS1, regulatory factors involved in sterol control of transcription and in cellular stress response. In this study, 11 different MBTPS2 missense mutations detected in patients from 13 unrelated families were correlated with the clinical phenotype, with their effect on cellular growth in media without lipids, and their potential role for sterol control of transcription. Seven variants were novel [c.774C>G (p.I258M); c.758G>C (p.G253A); c.686T>C (p.F229S); c.1427T>C (p.L476S); c.1430A>T (p.D477V); c.1499G>A (p.G500D); c.1538T>C (p.L513P)], four had previously been reported in unrelated sibships [c.261G>A (p.M87I); c.1286G>A (p.R429H); c.1424T>C (p.F475S); c.1523A>G (p.N508S)]. In the enzyme, the mutations cluster in transmembrane domains. Amino-acid exchanges near the active site are more detrimental to functionality of the enzyme and, clinically, associated with more severe phenotypes. In male patients, a genotypephenotype correlation begins to emerge, linking the site of the mutation in MBTPS2 with the clinical outcome described as IFAP syndrome with or without BRESHECK syndrome, keratosis follicularis spinulosa decalvans, X-linked, Olmsted syndrome, or possibly further X-linked traits with an oculocutaneous component.
  •  
3.
  • Crnkovic, Ivica, et al. (författare)
  • Guest Editorial
  • 2007
  • Ingår i: Journal of Systems and Software. - 0164-1212. ; 80:5, s. 641-642
  • Tidskriftsartikel (övrigt vetenskapligt)
  •  
4.
  • Haiman, Christopher A., et al. (författare)
  • A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer
  • 2011
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1546-1718. ; 43:12, s. 61-1210
  • Tidskriftsartikel (refereegranskat)abstract
    • Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 x 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 x 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 x 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.
  •  
5.
  • Heinz, Lisa, et al. (författare)
  • Mutations in SULT2B1 Cause Autosomal-Recessive Congenital Ichthyosis in Humans
  • 2017
  • Ingår i: American Journal of Human Genetics. - Cell Press. - 0002-9297. ; 100:6, s. 926-939
  • Tidskriftsartikel (refereegranskat)abstract
    • Ichthyoses are a clinically and genetically heterogeneous group of genodermatoses associated with abnormal scaling of the skin over the whole body. Mutations in nine genes are known to cause non-syndromic forms of autosomal-recessive congenital ichthyosis (ARCI). However, not all genetic causes for ARCI have been discovered to date. Using whole-exome sequencing (WES) and multigene panel screening, we identified 6 ARCI-affected individuals from three unrelated families with mutations in Sulfotransferase family 2B member 1 (SULT2B1), showing their causative association with ARCI. Cytosolic sulfotransferases form a large family of enzymes that are involved in the synthesis and metabolism of several steroids in humans. We identified four distinct mutations including missense, nonsense, and splice site mutations. We demonstrated the loss of SULT2B1 expression at RNA and protein levels in keratinocytes from individuals with ARCI by functional analyses. Furthermore, we succeeded in reconstructing the morphologic skin alterations in a 3D organotypic tissue culture model with SULT2B1-deficient keratinocytes and fibroblasts. By thin layer chromatography (TLC) of extracts from these organotypic cultures, we could show the absence of cholesterol sulfate, the metabolite of SULT2B1, and an increased level of cholesterol, indicating a disturbed cholesterol metabolism of the skin upon loss-of-function mutation in SULT2B1. In conclusion, our study reveals an essential role for SULT2B1 in the proper development of healthy human skin. Mutation in SULT2B1 leads to an ARCI phenotype via increased proliferation of human keratinocytes, thickening of epithelial layers, and altered epidermal cholesterol metabolism.
6.
  • Jiang, Xia, et al. (författare)
  • Shared heritability and functional enrichment across six solid cancers
  • 2019
  • Ingår i: Nature Communications. - 2041-1723. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10−8), breast and ovarian cancer (rg = 0.24, p = 7 × 10−5), breast and lung cancer (rg = 0.18, p =1.5 × 10−6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10−4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis. © 2019, The Author(s).
7.
  • Law, Philip J., et al. (författare)
  • Association analyses identify 31 new risk loci for colorectal cancer susceptibility
  • 2019
  • Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.
8.
  • Lehofer, Bernhard, et al. (författare)
  • High Hydrostatic Pressure Induces a Lipid Phase Transition and Molecular Rearrangements in Low-Density Lipoprotein Nanoparticles
  • 2018
  • Ingår i: Particle and Particle Systems Characterization. - John Wiley and Sons Inc.. - 0934-0866. ; 35:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Low-density lipoproteins (LDL) are natural lipid transporter in human plasma whose chemically modified forms contribute to the progression of atherosclerosis and cardiovascular diseases accounting for a vast majority of deaths in westernized civilizations. For the development of new treatment strategies, it is important to have a detailed picture of LDL nanoparticles on a molecular basis. Through the combination of X-ray and neutron small-angle scattering (SAS) techniques with high hydrostatic pressure (HHP) this study describes structural features of normolipidemic, triglyceride-rich and oxidized forms of LDL. Due to the different scattering contrasts for X-rays and neutrons, information on the effects of HHP on the internal structure determined by lipid rearrangements and changes in particle shape becomes accessible. Independent pressure and temperature variations provoke a phase transition in the lipid core domain. With increasing pressure an interrelated anisotropic deformation and flattening of the particle are induced. All LDL nanoparticles maintain their structural integrity even at 3000 bar and show a reversible response toward pressure variations. The present work depicts the complementarity of pressure and temperature as independent thermodynamic parameters and introduces HHP as a tool to study molecular assembling and interaction processes in distinct lipoprotein particles in a nondestructive manner.
9.
  • Locke, Adam E, et al. (författare)
  • Genetic studies of body mass index yield new insights for obesity biology
  • 2015
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-206
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P &lt; 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for &gt;20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
10.
  • Moller, Anders Pape, et al. (författare)
  • Clutch-size variation in Western Palaearctic secondary hole-nesting passerine birds in relation to nest box design
  • 2014
  • Ingår i: Methods in Ecology and Evolution. - British Ecology Society / John Wiley & Sons, Inc.. - 2041-210X. ; 5:4, s. 353-362
  • Tidskriftsartikel (refereegranskat)abstract
    • Secondary hole-nesting birds that do not construct nest holes themselves and hence regularly breed in nest boxes constitute important model systems for field studies in many biological disciplines with hundreds of scientists and amateurs involved. Those research groups are spread over wide geographic areas that experience considerable variation in environmental conditions, and researchers provide nest boxes of varying designs that may inadvertently introduce spatial and temporal variation in reproductive parameters. We quantified the relationship between mean clutch size and nest box size and material after controlling for a range of environmental variables in four of the most widely used model species in the Western Palaearctic: great tit Parus major, blue tit Cyanistes caeruleus, pied flycatcher Ficedula hypoleuca and collared flycatcher F.albicollis from 365 populations and 79610 clutches. Nest floor area and nest box material varied non-randomly across latitudes and longitudes, showing that scientists did not adopt a random box design. Clutch size increased with nest floor area in great tits, but not in blue tits and flycatchers. Clutch size of blue tits was larger in wooden than in concrete nest boxes. These findings demonstrate that the size of nest boxes and material used to construct nest boxes can differentially affect clutch size in different species. The findings also suggest that the nest box design may affect not only focal species, but also indirectly other species through the effects of nest box design on productivity and therefore potentially population density and hence interspecific competition.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 18
  • [1]2Nästa
Åtkomst
fritt online (6)
Typ av publikation
tidskriftsartikel (17)
forskningsöversikt (1)
Typ av innehåll
refereegranskat (16)
övrigt vetenskapligt (2)
Författare/redaktör
Montgomery, Grant W. ... (6)
Chang-Claude, Jenny (5)
Haiman, Christopher ... (5)
Giles, Graham G (5)
Le Marchand, Loïc (5)
Nevanlinna, Heli (4)
visa fler...
Blomqvist, Carl, (4)
Schumacher, Fredrick ... (4)
John, Esther M (4)
Martin, Nicholas G., (4)
Chasman, Daniel I., (4)
Peto, Julian (4)
Brauch, Hiltrud (4)
Cox, Angela (4)
Easton, Douglas F. (4)
Greco, Dario (3)
Henderson, Brian E (3)
Berndt, Sonja I (3)
Chanock, Stephen J (3)
Travis, Ruth C (3)
Amin, Najaf, (3)
Teumer, Alexander, (3)
Gudnason, Vilmundur, (3)
Hofman, Albert, (3)
Homuth, Georg, (3)
Severi, Gianluca, (3)
Magnusson, Patrik K ... (3)
Eccles, Diana (3)
Fletcher, Olivia (3)
Southey, Melissa C. (3)
Schmidt, Marjanka K. (3)
Hamann, Ute (3)
Hein, Rebecca (3)
Margolin, Sara (3)
Mannermaa, Arto (3)
Wang, Xianshu (3)
Baglietto, Laura (3)
Kraft, Peter (3)
Hall, Per (3)
Liu, Jianjun (3)
Hunter, David J. (3)
Pharoah, Paul D. P. (3)
Salomaa, Veikko (3)
Mangino, Massimo (3)
Gieger, Christian (3)
Nyholt, Dale R. (3)
Kaprio, Jaakko (3)
Jarvelin, Marjo-Riit ... (3)
Thorleifsson, Gudmar (3)
Feitosa, Mary F. (3)
visa färre...
Lärosäte
Lunds universitet (10)
Uppsala universitet (10)
Karolinska Institutet (10)
Göteborgs universitet (4)
Umeå universitet (4)
Högskolan Dalarna (2)
visa fler...
Mälardalens högskola (1)
Linköpings universitet (1)
visa färre...
Språk
Engelska (18)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (13)
Naturvetenskap (4)
Teknik (2)
Samhällsvetenskap (1)

År

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy