SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Homuth Georg) "

Sökning: WFRF:(Homuth Georg)

  • Resultat 31-40 av 52
  • Föregående 123[4]56Nästa
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
31.
  • Karasik, David, et al. (författare)
  • Disentangling the genetics of lean mass
  • 2019
  • Ingår i: American Journal of Clinical Nutrition. - Oxford University Press. - 0002-9165 .- 1938-3207. ; 109:2, s. 276-287
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>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.</p>
  •  
32.
  • Kolz, Melanie, et al. (författare)
  • Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations
  • 2009
  • Ingår i: PLoS genetics. - 1553-7404. ; 5:6, s. e1000504
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Elevated serum uric acid levels cause gout and are a risk factor for cardiovascular disease and diabetes. To investigate the polygenetic basis of serum uric acid levels, we conducted a meta-analysis of genome-wide association scans from 14 studies totalling 28,141 participants of European descent, resulting in identification of 954 SNPs distributed across nine loci that exceeded the threshold of genome-wide significance, five of which are novel. Overall, the common variants associated with serum uric acid levels fall in the following nine regions: <em>SLC2A9</em> (p = 5.2×10<sup>−201</sup>), <em>ABCG2</em> (p = 3.1×10<sup>−26</sup>), <em>SLC17A1</em> (p = 3.0×10<sup>−14</sup>), <em>SLC22A11</em> (p = 6.7×10<sup>−14</sup>), <em>SLC22A12</em> (p = 2.0×10<sup>−9</sup>), <em>SLC16A9</em> (p = 1.1×10<sup>−8</sup>), <em>GCKR</em> (p = 1.4×10<sup>−9</sup>), <em>LRRC16A</em> (p = 8.5×10<sup>−9</sup>), and near <em>PDZK1</em> (p = 2.7×10<sup>−9</sup>). Identified variants were analyzed for gender differences. We found that the minor allele for rs734553 in <em>SLC2A9</em> has greater influence in lowering uric acid levels in women and the minor allele of rs2231142 in <em>ABCG2</em> elevates uric acid levels more strongly in men compared to women. To further characterize the identified variants, we analyzed their association with a panel of metabolites. rs12356193 within <em>SLC16A9</em> was associated with DL-carnitine (p = 4.0×10<sup>−26</sup>) and propionyl-L-carnitine (p = 5.0×10<sup>−8</sup>) concentrations, which in turn were associated with serum UA levels (p = 1.4×10<sup>−57</sup> and p = 8.1×10<sup>−54</sup>, respectively), forming a triangle between SNP, metabolites, and UA levels. Taken together, these associations highlight additional pathways that are important in the regulation of serum uric acid levels and point toward novel potential targets for pharmacological intervention to prevent or treat hyperuricemia. In addition, these findings strongly support the hypothesis that transport proteins are key in regulating serum uric acid levels.</p>
  •  
33.
  • Moayyeri, Alireza, et al. (författare)
  • Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium
  • 2014
  • Ingår i: Human Molecular Genetics. - Oxford University Press. - 0964-6906. ; 23:11, s. 3054-3068
  • Tidskriftsartikel (refereegranskat)abstract
    • Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
34.
  • Moayyeri, Alireza, et al. (författare)
  • Genetic determinants of heel bone properties : genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium
  • 2014
  • Ingår i: Human Molecular Genetics. - 0964-6906 .- 1460-2083. ; 23:11, s. 3054-3068
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P &lt; 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P &lt; 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P &lt; 5 x 10(-6) also had the expected direction of association with any fracture (P &lt; 0.05), including three SNPs with P &lt; 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.</p>
  •  
35.
  • Newton-Cheh, Christopher, et al. (författare)
  • Genome-wide association study identifies eight loci associated with blood pressure
  • 2009
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 41:6, s. 666-676
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (<em>N</em> ≤ 71,225 European ancestry, <em>N</em> ≤ 12,889 Indian Asian ancestry) and <em>in silico</em> comparison (CHARGE consortium, <em>N</em> = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the <em>CYP17A1</em> (<em>P</em> = 7 × 10<sup>−24</sup>), <em>CYP1A2</em> (<em>P</em> = 1 × 10<sup>−23</sup>), <em>FGF5</em> (<em>P</em> = 1 × 10<sup>−21</sup>), <em>SH2B3</em> (<em>P</em> = 3 × 10<sup>−18</sup>), <em>MTHFR</em> (<em>P</em> = 2 × 10<sup>−13</sup>), <em>c10orf107</em> (<em>P</em> = 1 × 10<sup>−9</sup>), <em>ZNF652</em> (<em>P</em> = 5 × 10<sup>−9</sup>) and <em>PLCD3</em> (<em>P</em> = 1 × 10<sup>−8</sup>) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.</p>
  •  
36.
  • Obeidat, Ma'en, et al. (författare)
  • A Comprehensive Evaluation of Potential Lung Function Associated Genes in the SpiroMeta General Population Sample
  • 2011
  • Ingår i: PLoS ONE. - 1932-6203 .- 1932-6203. ; 6:5, s. e19382
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Rationale: </strong></p> <p>Lung function measures are heritable traits that predict population morbidity and mortality and are essential for the diagnosis of chronic obstructive pulmonary disease (COPD). Variations in many genes have been reported to affect these traits, but attempts at replication have provided conflicting results. Recently, we undertook a meta-analysis of Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general population (the SpiroMeta consortium).</p> <p><strong>Objectives:</strong></p> <p>To comprehensively analyse previously reported genetic associations with lung function measures, and to investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in a large population sample.</p> <p><strong>Methods:</strong></p> <p>We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/-10 kb), after conducting a systematic review of the literature in the PubMed database for genetic association studies reporting lung function associations.</p> <p><strong>Results:</strong></p> <p>The analysis included 16,936 genotyped and imputed SNPs. No loci showed overall significant association for FEV1 or FEV1/FVC traits using a carefully defined significance threshold of 1.3 x 10(-5). The most significant loci associated with FEV1 include SNPs tagging MACROD2 (P = 6.81 x 10(-5)), CNTN5 (P = 4.37 x 10(-4)), and TRPV4 (P = 1.58 x 10(-3)). Among ever-smokers, SERPINA1 showed the most significant association with FEV1 (P = 8.41 x 10(-5)), followed by PDE4D (P = 1.22 x 10(-4)). The strongest association with FEV1/FVC ratio was observed with ABCC1 (P = 4.38 x 10(-4)), and ESR1 (P = 5.42 x 10(-4)) among ever-smokers.</p> <p><strong>Conclusions: </strong></p> <p>Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population. Common SERPINA1 polymorphisms may affect FEV1 among smokers in the general population.</p>
  •  
37.
  • Parsa, Afshin, et al. (författare)
  • Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function
  • 2013
  • Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 24:12, s. 2105-2117
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency &gt;5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.</p>
  •  
38.
  • Pattaro, Cristian, et al. (författare)
  • Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function
  • 2012
  • Ingår i: PLoS Genetics. - 1553-7390. ; 8:3, s. e1002584
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genomewide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.</p>
  •  
39.
  • Repapi, Emmanouela, et al. (författare)
  • Genome-wide association study identifies five loci associated with lung function.
  • 2010
  • Ingår i: Nature genetics. - 1546-1718. ; 42:1, s. 36-44
  • Tidskriftsartikel (refereegranskat)abstract
    • Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 x 10(-12)), 4q24 in GSTCD (2.18 x 10(-23)), 5q33 in HTR4 (P = 4.29 x 10(-9)), 6p21 in AGER (P = 3.07 x 10(-15)) and 15q23 in THSD4 (P = 7.24 x 10(-15)). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.
  •  
40.
  • Repapi, Emmanouela, et al. (författare)
  • Genome-wide association study identifies five loci associated with lung function
  • 2010
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 42:1, s. 36-44
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV<sub>1</sub>) and the ratio of FEV<sub>1</sub> to forced vital capacity (FVC) in the SpiroMeta consortium (<em>n</em> = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (<em>n</em> ≤ 32,184 additional individuals) and <em>in silico</em> summary association data from the CHARGE Consortium (<em>n</em> = 21,209) and the Health 2000 survey (<em>n</em> ≤ 883). We confirmed the reported locus at 4q31 and identified associations with FEV<sub>1</sub> or FEV<sub>1</sub>/FVC and common variants at five additional loci: 2q35 in <em>TNS1</em> (<em>P</em> = 1.11 × 10<sup>−12</sup>), 4q24 in <em>GSTCD</em> (2.18 × 10<sup>−23</sup>), 5q33 in <em>HTR4</em> (<em>P</em> = 4.29 × 10<sup>−9</sup>), 6p21 in <em>AGER</em> (<em>P</em> = 3.07 × 10<sup>−15</sup>) and 15q23 in <em>THSD4</em> (<em>P</em> = 7.24 × 10<sup>−15</sup>). mRNA analyses showed expression of <em>TNS1</em>, <em>GSTCD</em>, <em>AGER</em>, <em>HTR4</em> and <em>THSD4</em> in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.</p>
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 31-40 av 52
  • Föregående 123[4]56Nästa
Åtkomst
fritt online (16)
Typ av publikation
tidskriftsartikel (52)
Typ av innehåll
refereegranskat (52)
övrigt vetenskapligt (3)
Författare/redaktör
Homuth, Georg (52)
Teumer, Alexander (36)
Hayward, Caroline (36)
Hofman, Albert (35)
Gudnason, Vilmundur (34)
Campbell, Harry (32)
visa fler...
Harris, Tamara B. (31)
Uitterlinden, Andre ... (30)
Mangino, Massimo (27)
Gieger, Christian (26)
Jarvelin, Marjo-Riit ... (26)
Feitosa, Mary F. (25)
Esko, Tonu (25)
Rivadeneira, Fernand ... (24)
Luan, Jian'an (24)
Polasek, Ozren (24)
Illig, Thomas (24)
Ohlsson, Claes (24)
Montgomery, Grant W. (23)
Launer, Lenore J. (23)
Wright, Alan F. (23)
Amin, Najaf (22)
Psaty, Bruce M. (22)
Van Duijn, Cornelia ... (22)
Wareham, Nicholas J (22)
Kuusisto, Johanna, (22)
Chasman, Daniel I., (22)
Kutalik, Zoltan (22)
Zhao, Jing Hua (22)
Vitart, Veronique (22)
Lind, Lars, (21)
Soranzo, Nicole (21)
Johnson, Toby (21)
Prokopenko, Inga (21)
McArdle, Wendy L. (21)
Gyllensten, Ulf (21)
Estrada, Karol (20)
Sanna, Serena (20)
Hottenga, Jouke-Jan (19)
Laakso, Markku, (19)
Salomaa, Veikko (19)
Peters, Annette (19)
Lorentzon, Mattias, (19)
Jackson, Anne U. (19)
Heard-Costa, Nancy L ... (19)
Thorleifsson, Gudmar (19)
Morris, Andrew P. (19)
Hicks, Andrew A. (19)
Collins, Francis S. (19)
Pramstaller, Peter P ... (19)
visa färre...
Lärosäte
Uppsala universitet (29)
Göteborgs universitet (13)
Lunds universitet (9)
Umeå universitet (8)
Karolinska Institutet (8)
Linköpings universitet (1)
Språk
Engelska (52)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (52)
Naturvetenskap (4)

År

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy