SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Aspelund Thor) "

Sökning: WFRF:(Aspelund Thor)

  • Resultat 1-10 av 43
  • [1]2345Nästa
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Allen, Hana Lango, et al. (författare)
  • Hundreds of variants clustered in genomic loci and biological pathways affect human height.
  • 2010
  • Ingår i: Nature. - 1476-4687. ; 467:7317, s. 832-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits(1), but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait(2,3). The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
  •  
2.
  • Artigas Soler, María, et al. (författare)
  • Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
  • 2011
  • Ingår i: Nature genetics. - 1546-1718. ; 43:11, s. 1082-90
  • Tidskriftsartikel (refereegranskat)abstract
    • Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
  •  
3.
  • Boeger, Carsten A., et al. (författare)
  • CUBN Is a Gene Locus for Albuminuria
  • 2011
  • Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 22:3, s. 555-570
  • Tidskriftsartikel (refereegranskat)abstract
    • Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 x 10(-11)) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.
  •  
4.
  • Carlsen, Hanne Krage, et al. (författare)
  • Respiratory health among professionals exposed to extreme SO2 levels from a volcanic eruption.
  • 2019
  • Ingår i: Scandinavian journal of work, environment & health. - 1795-990X. ; 45:3, s. 312-5
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective The Holuhraun eruption of fall and winter 2014-15 produced large amounts of sulfur dioxide (SO 2). The aim of this study was to determine if exposure to extreme SO 2levels affected the health of individuals working at the eruption site. Methods During January‒March 2015, earth scientists, technicians, and law enforcement personnel who were about to work at the eruption site were invited to a respiratory health examination. Symptom reports and lung function measures, forced expiratory volume in one second (FEV 1) and forced vital capacity (FVC) were collected before and after an eruption site visit. Those with previous exposure (N=27) reported symptoms retrospectively. Results Altogether, 41 individuals were invited to participate, 32 underwent a clinical examination at a hospital respiratory health clinic (baseline); 27 reported symptoms during earlier visits to the eruption site (retrospective symptom reports), 17 were re-examined 1-6 days after visiting the eruption site (follow-up). All participants' lung function was within normal range both before and after exposure. At baseline, average FEV 1was 107.4% of predicted versus 106.6 at follow-up (P =0.82); average FVC was 107.0% of predicted at baseline versus 107.4% at follow-up (P=0.35). Eye and nasal irritation were more frequently reported during eruption site exposure by 24% versus 6% (P =0.37) for both. Conclusion Although "healthy-worker" effects cannot be excluded, our data indicate that SO 2exposure was associated with relatively mild and transient respiratory symptoms with no clinical signs of airway inflammation or airway obstruction.
  •  
5.
  • Chasman, Daniel I., et al. (författare)
  • Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function
  • 2012
  • Ingår i: Human Molecular Genetics. - 0964-6906 .- 1460-2083. ; 21:24, s. 5329-5343
  • Tidskriftsartikel (refereegranskat)abstract
    • In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P 5.6 10(9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 10(4)2.2 10(7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.
  •  
6.
  • Dickerman, Barbra A., et al. (författare)
  • Midlife metabolic factors and prostate cancer risk in later life
  • 2018
  • Ingår i: International Journal of Cancer. - Hoboken, USA : John Wiley & Sons. - 0020-7136. ; 142:6, s. 1166-1173
  • Tidskriftsartikel (refereegranskat)abstract
    • Metabolic syndrome is associated with several cancers, but evidence for aggressive prostate cancer is sparse. We prospectively investigated the influence of metabolic syndrome and its components on risk of total prostate cancer and measures of aggressive disease in a cohort of Icelandic men. Men in the Reykjavik Study (n = 9,097, enrolled 1967-1987) were followed for incident (n = 1,084 total; n = 378 advanced; n = 148 high-grade) and fatal (n = 340) prostate cancer until 2014. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for (1) measured metabolic factors at cohort entry (body mass index (BMI), blood pressure, triglycerides, fasting blood glucose) and (2) a metabolic syndrome score (range 0-4) combining the risk factors: BMI ≥30 kg/m2 ; systolic blood pressure (SBP) ≥130 or diastolic blood pressure (DBP) ≥85 mm Hg or taking antihypertensives; triglycerides ≥150 mg/dl; fasting blood glucose ≥100 mg/dl or self-reported type 2 diabetes. Hypertension and type 2 diabetes were associated with a higher risk of total, advanced, high-grade, and fatal prostate cancer, independent of BMI. Neither BMI nor triglycerides were associated with prostate cancer risk. Higher metabolic syndrome score (3-4 vs 0) was associated with a higher risk of fatal prostate cancer (HR 1.55; 95% CI: 0.89, 2.69; p trend = 0.08), although this finding was not statistically significant. Our findings suggest a positive association between midlife hypertension and diabetes and risk of total and aggressive prostate cancer. Further, metabolic syndrome as a combination of factors was associated with an increased risk of fatal prostate cancer.
  •  
7.
  • Ehret, Georg B., et al. (författare)
  • Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk
  • 2011
  • Ingår i: Nature. - Nature Publishing Group. - 0028-0836. ; 478:7367, s. 103-109
  • Tidskriftsartikel (refereegranskat)abstract
    • Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
  •  
8.
  • Elks, Cathy E, et al. (författare)
  • Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
  • 2010
  • Ingår i: Nature genetics. - 1546-1718. ; 42:12, s. 1077-U73
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P &lt; 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P &lt; 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
  •  
9.
  •  
10.
  • Estrada, Karol, et al. (författare)
  • Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
  • 2012
  • Ingår i: Nature genetics. - 1546-1718. ; 44:5, s. 491-501
  • Tidskriftsartikel (refereegranskat)abstract
    • Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P &lt; 5 x 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P &lt; 5 x 10(-4), Bonferroni corrected), of which six reached P &lt; 5 x 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 43
  • [1]2345Nästa
Åtkomst
fritt online (10)
Typ av publikation
tidskriftsartikel (43)
Typ av innehåll
refereegranskat (43)
Författare/redaktör
Aspelund, Thor (43)
Gudnason, Vilmundur, (37)
Harris, Tamara B. (31)
Launer, Lenore J., (22)
Eiriksdottir, Gudny (22)
Hofman, Albert, (21)
visa fler...
Uitterlinden, Andre ... (18)
Hayward, Caroline (18)
Campbell, Harry (18)
Smith, Albert V., (17)
Rivadeneira, Fernand ... (17)
Boerwinkle, Eric (17)
Rudan, Igor (17)
Polasek, Ozren (16)
Wilson, James F. (16)
Van Duijn, Cornelia ... (15)
Vitart, Veronique (15)
Wright, Alan F. (15)
Ridker, Paul M., (14)
Chasman, Daniel I., (14)
Shuldiner, Alan R. (14)
Pramstaller, Peter P ... (14)
Liu, Yongmei (14)
Wild, Sarah H. (13)
Psaty, Bruce M., (12)
Oostra, Ben A. (12)
Wichmann, H. Erich (12)
Gyllensten, Ulf, (12)
Teumer, Alexander, (11)
Ferrucci, Luigi, (11)
Rotter, Jerome I., (11)
Johansson, Åsa, (11)
Gieger, Christian (11)
Esko, Tonu (11)
Prokopenko, Inga (11)
Igl, Wilmar, (11)
Illig, Thomas (11)
Kolcic, Ivana (11)
Zgaga, Lina (11)
Fox, Caroline S. (11)
Metspalu, Andres (11)
Viikari, Jorma (10)
Amin, Najaf, (10)
Voelzke, Henry, (10)
Wareham, Nicholas J. (10)
Heid, Iris M. (10)
Kutalik, Zoltan (10)
Bergmann, Sven (10)
Loos, Ruth J. F. (10)
Hwang, Shih-Jen (10)
visa färre...
Lärosäte
Uppsala universitet (27)
Lunds universitet (16)
Karolinska Institutet (16)
Göteborgs universitet (11)
Örebro universitet (7)
Umeå universitet (4)
visa fler...
Luleå tekniska universitet (1)
Stockholms universitet (1)
Högskolan Dalarna (1)
visa färre...
Språk
Engelska (43)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (42)
Naturvetenskap (5)
Teknik (1)

År

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy