SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Alves Alexessander Couto) "

Sökning: WFRF:(Alves Alexessander Couto)

  • Resultat 1-10 av 21
  • [1]23Nästa
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Kanoni, Stavroula, et al. (författare)
  • Analysis with the exome array identifies multiple new independent variants in lipid loci
  • 2016
  • Ingår i: Human Molecular Genetics. - Oxford University Press. - 0964-6906. ; 25:18, s. 4094-4106
  • Tidskriftsartikel (refereegranskat)abstract
    • It has been hypothesized that low frequency (1-5% minor allele frequency (MAF)) and rare (<1% MAF) variants with large effect sizes may contribute to the missing heritability in complex traits. Here, we report an association analysis of lipid traits (total cholesterol, LDL-cholesterol, HDL-cholesterol triglycerides) in up to 27 312 individuals with a comprehensive set of low frequency coding variants (ExomeChip), combined with conditional analysis in the known lipid loci. No new locus reached genome-wide significance. However, we found a new lead variant in 26 known lipid association regions of which 16 were > 1000-fold more significant than the previous sentinel variant and not in close LD (six had MAF < 5%). Furthermore, conditional analysis revealed multiple independent signals (ranging from 1 to 5) in a third of the 98 lipid loci tested, including rare variants. Addition of our novel associations resulted in between 1.5- and 2.5-fold increase in the proportion of heritability explained for the different lipid traits. Our findings suggest that rare coding variants contribute to the genetic architecture of lipid traits.
  •  
2.
  • Paternoster, Lavinia, et al. (författare)
  • Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis.
  • 2012
  • Ingår i: Nature genetics. - 1546-1718. ; 44:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies. Three SNPs reached genome-wide significance in the discovery and replication cohorts combined, including rs479844 upstream of OVOL1 (odds ratio (OR) = 0.88, P = 1.1 × 10(-13)) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 × 10(-9)), both of which are near genes that have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster at 5q31.1 (OR = 1.11, P = 3.8 × 10(-8)). We also replicated association with the FLG locus and with two recently identified association signals at 11q13.5 (rs7927894; P = 0.008) and 20q13.33 (rs6010620; P = 0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis.
  •  
3.
  • Ried, Janina S., et al. (författare)
  • A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
  • 2016
  • Ingår i: Nature Communications. - Nature Publishing Group. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
4.
  • van der Valk, Ralf J P, et al. (författare)
  • A novel common variant in DCST2 is associated with length in early life and height in adulthood.
  • 2015
  • Ingår i: Human molecular genetics. - 1460-2083. ; 24:4, s. 1155-68
  • Tidskriftsartikel (refereegranskat)abstract
    • Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P &lt; 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
5.
  • Albrecht, Eva, et al. (författare)
  • Telomere length in circulating leukocytes is associated with lung function and disease
  • 2014
  • Ingår i: European Respiratory Journal. - 0903-1936 .- 1399-3003. ; 43:4, s. 983-992
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in is (FEV1), forced vital capacity (PVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (beta= -0.0452, p= 0.024) as well as COPD (beta= -0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07 x 10(-7)), FVC (p=2.07 x 10(-5)), and FEV1/FVC (p =5.27 x 10(-3)). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.</p>
  •  
6.
  • Barrenäs, Fredrik, 1981-, et al. (författare)
  • Highly interconnected genes in disease-specific networks are enriched for disease-associated polymorphisms
  • 2012
  • Ingår i: Genome Biology. - 1474760X. ; 13:6, s. R46
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Complex diseases are associated with altered interactions between thousands of genes. We developed a novel method to identify and prioritize disease genes, which was generally applicable to complex diseases. RESULTS: We identified modules of highly interconnected genes in disease-specific networks derived from integrating gene-expression and protein interaction data. We examined if those modules were enriched for disease-associated single nucleotide polymorphisms (SNPs), and could be used to find novel genes for functional studies. First, we analyzed publicly available gene expression microarray and genome-wide association study (GWAS) data from 13, highly diverse, complex diseases. In each disease, highly interconnected genes formed modules, which were significantly enriched for genes harboring disease-associated SNPs. To test if such modules could be used to find novel genes for functional studies, we repeated the analyses using our own gene expression microarray and GWAS data from seasonal allergic rhinitis. We identified a novel gene, FGF2, whose relevance was supported by functional studies using combined siRNA-mediated knock-down and gene expression microarrays. The modules in the 13 complex diseases analyzed here tended to overlap and were enriched for pathways related to oncological, metabolic and inflammatory diseases. This suggested that this union of the modules would be associated with a general increase in susceptibility for complex diseases. Indeed, we found that this union was enriched with GWAS genes for 145 other complex diseases. CONCLUSIONS: Modules of highly interconnected complex disease genes were enriched for disease-associated SNPs, and could be used to find novel genes for functional studies.
7.
  • Barrenäs, Fredrik, et al. (författare)
  • Highly interconnected genes in disease-specific networks are enriched for disease-associated polymorphisms
  • 2012
  • Ingår i: Genome Biology. - BioMed Central. - 1465-6906 .- 1474-760X. ; 13:6, s. R46
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>BACKGROUND:</strong> Complex diseases are associated with altered interactions between thousands of genes. We developed a novel method to identify and prioritize disease genes, which was generally applicable to complex diseases.</p><p><strong>RESULTS:</strong> We identified modules of highly interconnected genes in disease-specific networks derived from integrating gene-expression and protein interaction data. We examined if those modules were enriched for disease-associated SNPs, and could be used to find novel genes for functional studies. First, we analyzed publicly available gene expression microarray and genome-wide association study (GWAS) data from 13, highly diverse, complex diseases. In each disease, highly interconnected genes formed modules, which were significantly enriched for genes harboring disease-associated SNPs. To test if such modules could be used to find novel genes for functional studies, we repeated the analyses using our own gene expression microarray and GWAS data from seasonal allergic rhinitis. We identified a novel gene, FGF2, whose relevance was supported by functional studies using combined small interfering RNA-mediated knock-down and gene expression microarrays. The modules in the 13 complex diseases analyzed here tended to overlap and were enriched for pathways related to oncological, metabolic and inflammatory diseases. This suggested that this union of the modules would be associated with a general increase in susceptibility for complex diseases. Indeed, we found that this union was enriched with GWAS genes for 145 other complex diseases.</p><p><strong>CONCLUSIONS:</strong> Modules of highly interconnected complex disease genes were enriched for disease-associated SNPs, and could be used to find novel genes for functional studies.</p>
  •  
8.
  • Buxton, Jessica L., et al. (författare)
  • Multiple Measures of Adiposity Are Associated with Mean Leukocyte Telomere Length in the Northern Finland Birth Cohort 1966
  • 2014
  • Ingår i: PLoS ONE. - 1932-6203 .- 1932-6203. ; 9:6, s. Art. no. e99133
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Studies of leukocyte telomere length (LTL) and adiposity have produced conflicting results, and the relationship between body mass index (BMI) and telomere length throughout life remains unclear. We therefore tested association of adult LTL measured in 5,598 participants with: i) childhood growth measures (BMI and age at adiposity rebound (AR)); ii) change in BMI from childhood to adulthood and iii) adult BMI, waist-to-hip ratio (WHR), body adiposity index (BAI). Childhood BMI at AR was positively associated with LTL at 31 years in women (P = 0.041). Adult BMI and WHR in both men (P = 0.025 and P = 0.049, respectively) and women (P = 0.029 and P = 0.008, respectively), and BAI in women (P = 0.021) were inversely associated with LTL at 31 years. An increase in standardised BMI between early childhood and adulthood was associated with shorter adult LTL in women (P = 0.008). We show that LTL is inversely associated with multiple measures of adiposity in both men and women. Additionally, BMI increase in women from childhood to adulthood is associated with shorter telomeres at age 31, potentially indicating accelerated biological ageing.</p>
  •  
9.
  • Couto Alves, Alexessander, et al. (författare)
  • Dysregulation of Complement System and CD4+T Cell Activation Pathways Implicated in Allergic Response
  • 2013
  • Ingår i: PLoS ONE. - Public Library of Science. - 1932-6203 .- 1932-6203. ; 8:10
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Allergy is a complex disease that is likely to involve dysregulated CD4+ T cell activation. Here we propose a novel methodology to gain insight into how coordinated behaviour emerges between disease-dysregulated pathways in response to pathophysiological stimuli. Using peripheral blood mononuclear cells of allergic rhinitis patients and controls cultured with and without pollen allergens, we integrate CD4+ T cell gene expression from microarray data and genetic markers of allergic sensitisation from GWAS data at the pathway level using enrichment analysis; implicating the complement system in both cellular and systemic response to pollen allergens. We delineate a novel disease network linking T cell activation to the complement system that is significantly enriched for genes exhibiting correlated gene expression and protein-protein interactions, suggesting a tight biological coordination that is dysregulated in the disease state in response to pollen allergen but not to diluent. This novel disease network has high predictive power for the gene and protein expression of the Th2 cytokine profile (<em>IL-4, IL-5, IL-10, IL-13</em>) and of the Th2 master regulator (<em>GATA3</em>), suggesting its involvement in the early stages of CD4+ T cell differentiation. Dissection of the complement system gene expression identifies 7 genes specifically associated with atopic response to pollen, including <em>C1QR1, CFD, CFP, ITGB2</em>, <em>ITGAX</em> and confirms the role of <em>C3AR1</em> and <em>C5AR1.</em> Two of these genes (<em>ITGB2</em> and <em>C3AR1)</em> are also implicated in the network linking complement system to T cell activation, which comprises 6 differentially expressed genes. <em>C3AR1</em> is also significantly associated with allergic sensitisation in GWAS data.</p>
  •  
10.
  • Kanoni, Stavroula, et al. (författare)
  • Analysis with the exome array identifies multiple new independent variants in lipid loci
  • 2016
  • Ingår i: Human Molecular Genetics. - 0964-6906 .- 1460-2083. ; 25:18, s. 4094-4106
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>It has been hypothesized that low frequency (1-5% minor allele frequency (MAF)) and rare (&lt;1% MAF) variants with large effect sizes may contribute to the missing heritability in complex traits. Here, we report an association analysis of lipid traits (total cholesterol, LDL-cholesterol, HDL-cholesterol triglycerides) in up to 27 312 individuals with a comprehensive set of low frequency coding variants (ExomeChip), combined with conditional analysis in the known lipid loci. No new locus reached genome-wide significance. However, we found a new lead variant in 26 known lipid association regions of which 16 were &gt;1000-fold more significant than the previous sentinel variant and not in close LD (six had MAF &lt;5%). Furthermore, conditional analysis revealed multiple independent signals (ranging from 1 to 5) in a third of the 98 lipid loci tested, including rare variants. Addition of our novel associations resulted in between 1.5- and 2.5-fold increase in the proportion of heritability explained for the different lipid traits. Our findings suggest that rare coding variants contribute to the genetic architecture of lipid traits.</p>
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 21
  • [1]23Nästa
Åtkomst
fritt online (13)
Typ av publikation
tidskriftsartikel (21)
Typ av innehåll
refereegranskat (21)
övrigt vetenskapligt (1)
Författare/redaktör
Jarvelin, Marjo-Riit ... (15)
Alves, Alexessander ... (13)
Gieger, Christian (12)
Scott, Robert A (10)
McCarthy, Mark I (9)
Salomaa, Veikko (9)
visa fler...
Mangino, Massimo (9)
Waldenberger, Melani ... (9)
Boomsma, Dorret I. (8)
Hofman, Albert (8)
Linneberg, Allan, (8)
Albrecht, Eva (8)
Metspalu, Andres (8)
van der Harst, Pim (8)
Franks, Paul W, (7)
Martin, Nicholas G. (7)
Deloukas, Panos (7)
Grarup, Niels, (7)
Hansen, Torben, (7)
Peters, Annette (7)
Samani, Nilesh J. (7)
Esko, Tonu (7)
Pouta, Anneli (7)
Wilson, James F. (7)
Müller-Nurasyid, Mar ... (7)
Kumari, Meena (7)
Kuh, Diana (6)
Trompet, Stella (6)
Hartman, Catharina A ... (6)
Hottenga, Jouke-Jan (6)
Jukema, J. Wouter (6)
Montgomery, Grant W. (6)
Uitterlinden, Andre ... (6)
Ahluwalia, Tarunveer ... (6)
Langenberg, Claudia (6)
Hamsten, Anders (6)
Lehtimäki, Terho, (6)
Willemsen, Gonneke (6)
Lorentzon, Mattias, (6)
Eriksson, Joel, (6)
Luan, Jian'an (6)
Hayward, Caroline (6)
Rayner, Nigel W. (6)
Campbell, Harry (6)
Eriksson, Johan G. (6)
Jula, Antti (6)
Widen, Elisabeth (6)
Wright, Alan F. (6)
Frayling, Timothy M. (6)
Nolte, Ilja M (6)
visa färre...
Lärosäte
Göteborgs universitet (6)
Umeå universitet (5)
Lunds universitet (5)
Uppsala universitet (5)
Karolinska Institutet (5)
Linköpings universitet (2)
visa fler...
Mittuniversitetet (2)
Chalmers tekniska högskola (1)
visa färre...
Språk
Engelska (21)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (21)
Samhällsvetenskap (1)

År

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy