SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Mitchell Braxton D.) "

Sökning: WFRF:(Mitchell Braxton D.)

  • Resultat 1-10 av 75
  • [1]234567...8Nästa
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Lanktree, Matthew B., et al. (författare)
  • Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height
  • 2011
  • Ingår i: American Journal of Human Genetics. - Cell Press. - 0002-9297. ; 88:1, s. 41443-41443
  • Tidskriftsartikel (refereegranskat)abstract
    • Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 x 10(-6)), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 x 10(-8)). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 x 10(-11)). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait.
  •  
2.
  • Willer, Cristen J., et al. (författare)
  • Discovery and refinement of loci associated with lipid levels
  • 2013
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1546-1718. ; 45:11, s. 1274-1274
  • Tidskriftsartikel (refereegranskat)abstract
    • Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
  •  
3.
  • den Hoed, Marcel, et al. (författare)
  • Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders
  • 2013
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1546-1718. ; 45:6, s. 621-631
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.
  •  
4.
  • Do, Ron, et al. (författare)
  • Common variants associated with plasma triglycerides and risk for coronary artery disease
  • 2013
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1546-1718. ; 45:11, s. 1345-1345
  • Tidskriftsartikel (refereegranskat)abstract
    • Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
  •  
5.
  • Saxena, Richa, et al. (författare)
  • Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
  • 2010
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1546-1718. ; 42:2, s. 75-142
  • Tidskriftsartikel (refereegranskat)abstract
    • Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620). We identify variants at the GIPR locus associated with 2- h glucose level (rs10423928, beta (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 x 10(-15)). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 x 10(-17); ratio of insulin to glucose area under the curve, P = 1.3 x 10(-16)) and diminished incretin effect (n = 804; P = 4.3 x 10(-4)). We also identified variants at ADCY5 (rs2877716, P = 4.2 x 10(-16)), VPS13C (rs17271305, P = 4.1 x 10(-8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18)).
  •  
6.
  • Saxena, Richa, et al. (författare)
  • Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci
  • 2012
  • Ingår i: American Journal of Human Genetics. - Cell Press. - 0002-9297. ; 90:3, s. 410-425
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with similar to 2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 x 10(-9)) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p < 2.4 x 10(-6)). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 x 10(-7)) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 x 10(-15)). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 x 10(-8)). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups.
  •  
7.
  • Malik, Rainer, et al. (författare)
  • Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes
  • 2018
  • Ingår i: Nature Genetics. - NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 50:4, s. 524-537
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke sub-types. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.</p>
  •  
8.
  •  
9.
  • Palmer, Nicholette D, et al. (författare)
  • A genome-wide association search for type 2 diabetes genes in African Americans.
  • 2012
  • Ingår i: PloS one. - 1932-6203. ; 7:1, s. e29202
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P&lt;0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P&lt;0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P&lt;2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P&lt;0.05) and reached more nominal levels of significance (P&lt;2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.</p>
10.
  • Palmer, Nicholette D, et al. (författare)
  • A genome-wide association search for type 2 diabetes genes in African Americans.
  • 2012
  • Ingår i: PLoS ONE. - San Francisco : Public Library of Science. - 1932-6203 .- 1932-6203. ; 7:1, s. e29202
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P&lt;0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P&lt;0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P&lt;2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P&lt;0.05) and reached more nominal levels of significance (P&lt;2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.</p>
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 75
  • [1]234567...8Nästa
Åtkomst
fritt online (16)
Typ av publikation
tidskriftsartikel (74)
forskningsöversikt (1)
Typ av innehåll
refereegranskat (74)
övrigt vetenskapligt (3)
Författare/redaktör
Mitchell, Braxton D. (74)
Psaty, Bruce M. (35)
Shuldiner, Alan R. (35)
Thorleifsson, Gudmar (34)
Hofman, Albert (33)
Thorsteinsdottir, Un ... (33)
visa fler...
Stefansson, Kari (33)
Van Duijn, Cornelia ... (32)
Harris, Tamara B. (32)
Wilson, James F. (32)
Rotter, Jerome I. (31)
Illig, Thomas (31)
Gudnason, Vilmundur (30)
Rivadeneira, Fernand ... (30)
Uitterlinden, Andre ... (29)
Hayward, Caroline (29)
Campbell, Harry (28)
Gieger, Christian (27)
Wareham, Nicholas J (26)
Boerwinkle, Eric (26)
Rudan, Igor (26)
Salomaa, Veikko (25)
Luan, Jian'an (25)
Loos, Ruth J. F. (25)
Tanaka, Toshiko (25)
Ferrucci, Luigi (24)
Langenberg, Claudia (24)
Ingelsson, Erik (24)
Johnson, Toby (24)
Zhao, Jing Hua (24)
Kuusisto, Johanna, (23)
Laakso, Markku, (23)
Jula, Antti (23)
Borecki, Ingrid B (23)
Kumari, Meena (23)
Khaw, Kay-Tee (22)
Oostra, Ben A. (22)
Wild, Sarah H. (22)
Lind, Lars, (21)
Feitosa, Mary F. (21)
Gyllensten, Ulf (21)
O'Connell, Jeffrey R ... (21)
Kivimaki, Mika (21)
Boehnke, Michael (20)
Lorentzon, Mattias, (20)
Zillikens, M. Carola (20)
Fox, Caroline S. (20)
Chambers, John C. (20)
Kooner, Jaspal S. (20)
Grallert, Harald (20)
visa färre...
Lärosäte
Lunds universitet (35)
Uppsala universitet (23)
Göteborgs universitet (22)
Umeå universitet (11)
Karolinska Institutet (11)
Språk
Engelska (75)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (74)
Naturvetenskap (3)
Teknik (1)

År

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy