Association Analysis

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Richard C Hamelin - One of the best experts on this subject based on the ideXlab platform.

  • Association Analysis identifies melampsora columbiana poplar leaf rust resistance snps
    PLOS ONE, 2013
    Co-Authors: Jonathan La Mantia, Shofiul Azam, Robert D. Guy, Carl J. Douglas, Shawn D. Mansfield, Jaroslav Klapstě, Yousry A Elkassaby, Richard C Hamelin
    Abstract:

    Populus species are currently being domesticated through intensive time- and resource-dependent programs for utilization in phytoremediation, wood and paper products, and conversion to biofuels. Poplar leaf rust disease can greatly reduce wood volume. Genetic resistance is effective in reducing economic losses but major resistance loci have been race-specific and can be readily defeated by the pathogen. Developing durable disease resistance requires the identification of non-race-specific loci. In the presented study, area under the disease progress curve was calculated from natural infection of Melampsora ×columbiana in three consecutive years. Association Analysis was performed using 412 P. trichocarpa clones genotyped with 29,355 SNPs covering 3,543 genes. We found 40 SNPs within 26 unique genes significantly associated (permutated P<0.05) with poplar rust severity. Moreover, two SNPs were repeated in all three years suggesting non-race-specificity and three additional SNPs were differentially expressed in other poplar rust interactions. These five SNPs were found in genes that have orthologs in Arabidopsis with functionality in pathogen induced transcriptome reprogramming, Ca2+/calmodulin and salicylic acid signaling, and tolerance to reactive oxygen species. The additive effect of non-R gene functional variants may constitute high levels of durable poplar leaf rust resistance. Therefore, these findings are of significance for speeding the genetic improvement of this long-lived, economically important organism.

Tobias J Weismüller - One of the best experts on this subject based on the ideXlab platform.

  • genome wide Association Analysis in primary sclerosing cholangitis identifies two non hla susceptibility loci
    Nature Genetics, 2011
    Co-Authors: Espen Melum, Andre Franke, Christoph Schramm, Tobias J Weismüller, Daniel Nils Gotthardt, Brian D Juran, Jon K Laerdahl, Verena Labi, Felix Offner, Einar Björnsson
    Abstract:

    Primary sclerosing cholangitis (PSC) is a chronic bile duct disease affecting 2.4–7.5% of individuals with inflammatory bowel disease. We performed a genome-wide Association Analysis of 2,466,182 SNPs in 715 individuals with PSC and 2,962 controls, followed by replication in 1,025 PSC cases and 2,174 controls. We detected non-HLA Associations at rs3197999 in MST1 and rs6720394 near BCL2L11 (combined P = 1.1 × 10−16 and P = 4.1 × 10−8, respectively).

  • genome wide Association Analysis in primary sclerosing cholangitis
    Gastroenterology, 2010
    Co-Authors: Tom H Karlsen, Espen Melum, Andre Franke, Christoph Schramm, Arthur Kaser, Johannes R Hov, Tobias Balschun, Benedicte A Lie, Annika Bergquist, Tobias J Weismüller
    Abstract:

    Background & Aims We aimed to characterize the genetic susceptibility to primary sclerosing cholangitis (PSC) by means of a genome-wide Association Analysis of single nucleotide polymorphism (SNP) markers. Methods A total of 443,816 SNPs on the Affymetrix SNP Array 5.0 (Affymetrix, Santa Clara, CA) were genotyped in 285 Norwegian PSC patients and 298 healthy controls. Associations detected in this discovery panel were re-examined in independent case-control panels from Scandinavia (137 PSC cases and 368 controls), Belgium/The Netherlands (229 PSC cases and 735 controls), and Germany (400 cases and 1832 controls). Results The strongest Associations were detected near HLA-B at chromosome 6p21 (rs3099844: odds ratio [OR], 4.8; 95% confidence interval [CI], 3.6–6.5; P = 2.6 × 10 −26 ; and rs2844559: OR, 4.7; 95% CI, 3.5–6.4; P = 4.2 × 10 −26 in the discovery panel). Outside the HLA complex, rs9524260 at chromosome 13q31 showed significant Associations in 3 of 4 study panels. Lentiviral silencing of glypican 6, encoded at this locus, led to the up-regulation of proinflammatory markers in a cholangiocyte cell line. Of 15 established ulcerative colitis susceptibility loci, significant replication was obtained at chromosomes 2q35 and 3p21 (rs12612347: OR, 1.26; 95% CI, 1.06–1.50; and rs3197999: OR, 1.22; 95% CI, 1.02–1.47, respectively), with circumstantial evidence supporting the G-protein–coupled bile acid receptor 1 and macrophage-stimulating 1 , respectively, as the likely disease genes. Conclusions Strong HLA Associations and a subset of genes involved in bile homeostasis and other inflammatory conditions constitute key components of the genetic architecture of PSC.

Ryk Ward - One of the best experts on this subject based on the ideXlab platform.

  • linkage and Association Analysis of angiotensin i converting enzyme ace gene polymorphisms with ace concentration and blood pressure
    American Journal of Human Genetics, 2001
    Co-Authors: Nourdine Bouzekri, Colin A Mckenzie, Lorraine Southam, Adebowale Adeyemo, Guangjie Chen, Amy Luke, Richard S. Cooper, Ryk Ward
    Abstract:

    Considerable effort has been expended to determine whether the gene for angiotensin I–converting enzyme (ACE) confers susceptibility to cardiovascular disease. In this study, we genotyped 13 polymorphisms in the ACE gene in 1,343 Nigerians from 332 families. To localize the genetic effect, we first performed linkage and Association Analysis of all the markers with ACE concentration. In multipoint variance-component Analysis, this region was strongly linked to ACE concentration (maximum LOD score 7.5). Likewise, most of the polymorphisms in the ACE gene were significantly associated with ACE ( P

  • linkage and Association Analysis of angiotensin i converting enzyme ace gene polymorphisms with ace concentration and blood pressure
    American Journal of Human Genetics, 2001
    Co-Authors: Nourdine Bouzekri, Colin A Mckenzie, Lorraine Southam, Adebowale Adeyemo, Guangjie Chen, Amy Luke, Richard S. Cooper, Robert C Elston, Ryk Ward
    Abstract:

    Considerable effort has been expended to determine whether the gene for angiotensin I–converting enzyme (ACE) confers susceptibility to cardiovascular disease. In this study, we genotyped 13 polymorphisms in the ACE gene in 1,343 Nigerians from 332 families. To localize the genetic effect, we first performed linkage and Association Analysis of all the markers with ACE concentration. In multipoint variance-component Analysis, this region was strongly linked to ACE concentration (maximum LOD score 7.5). Likewise, most of the polymorphisms in the ACE gene were significantly associated with ACE ( P

Francesca Luca - One of the best experts on this subject based on the ideXlab platform.

  • integrating molecular qtl data into genome wide genetic Association Analysis probabilistic assessment of enrichment and colocalization
    PLOS Genetics, 2017
    Co-Authors: Roger Piqueregi, Francesca Luca
    Abstract:

    We propose a novel statistical framework for integrating the result from molecular quantitative trait loci (QTL) mapping into genome-wide genetic Association Analysis of complex traits, with the primary objectives of quantitatively assessing the enrichment of the molecular QTLs in complex trait-associated genetic variants and the colocalizations of the two types of Association signals. We introduce a natural Bayesian hierarchical model that treats the latent Association status of molecular QTLs as SNP-level annotations for candidate SNPs of complex traits. We detail a computational procedure to seamlessly perform enrichment, fine-mapping and colocalization analyses, which is a distinct feature compared to the existing colocalization Analysis procedures in the literature. The proposed approach is computationally efficient and requires only summary-level statistics. We evaluate and demonstrate the proposed computational approach through extensive simulation studies and analyses of blood lipid data and the whole blood eQTL data from the GTEx project. In addition, a useful utility from our proposed method enables the computation of expected colocalization signals using simple characteristics of the Association data. Using this utility, we further illustrate the importance of enrichment Analysis on the ability to discover colocalized signals and the potential limitations of currently available molecular QTL data. The software pipeline that implements the proposed computation procedures, enloc, is freely available at https://github.com/xqwen/integrative.

  • integrating molecular qtl data into genome wide genetic Association Analysis probabilistic assessment of enrichment and colocalization
    bioRxiv, 2016
    Co-Authors: Roger Piqueregi, Francesca Luca
    Abstract:

    We propose a novel statistical framework for integrating genetic data from molecular quantitative trait loci (QTL) mapping into genome-wide genetic Association Analysis of complex traits, with the primary objectives of quantitatively assessing the enrichment of the molecular QTLs in complex trait-associated genetic variants and the colocalizations of the two types of Association signals. We introduce a natural Bayesian hierarchical model that treats the latent Association status of molecular QTLs as SNP-level annotations for candidate SNPs for complex traits. We detail a computational procedure to seamlessly perform enrichment, fine-mapping and colocalization analyses, which is a distinct feature compared to the existing colocalization Analysis procedures in the literature. The proposed approach is computationally efficient and requires only summary-level statistics. We evaluate and demonstrate the proposed computational approach through extensive simulation studies and the Analysis of blood lipid data and the whole blood eQTL data from the GTEx project. In addition, a useful utility from our proposed method enables the computation of expected colocalization signals, which is analogous to the power calculation in genetic Association studies. Using this utility, we further illustrate the importance of enrichment Analysis on the ability of discovering colocalized signals and the potential limitations of currently available molecular QTL data.

Jaesung Lee - One of the best experts on this subject based on the ideXlab platform.

  • novel sources of aus rice for zinc deficiency tolerance identified through Association Analysis using high density snp array
    Rice Science, 2018
    Co-Authors: Jaesung Lee, Matthias Wissuwa, Oscar B Zamora, Abdelbagi M Ismail
    Abstract:

    Abstract Zinc (Zn) deficiency is a major soil constraint limiting rice crop growth and yield, yet the genetic control of tolerance mechanisms is still poorly understood. Here, we presented promising loci and candidate genes conferring tolerance to Zn deficiency and identified through Association Analysis using a 365 K single nucleotide polymorphism (SNP) marker array in a diverse aus (semi-wild type rice) panel. Tolerant accessions exhibited higher growth rate with relatively rare stress symptoms. Two loci on chromosomes 7 and 9 were strongly associated with plant vigor under Zn deficiency at a peak-stress stage. Based on previous microarray data from the same experimental plots, we highlighted four candidate genes whose expressions were accompanied by significant genotype and/or environment effects under Zn deficiency. Network-gene ontology supported known tolerance mechanisms, such as ascorbic acid pathway, and also suggested the importance of photosynthesis genes to overcome Zn deficiency symptoms.

  • Novel Sources of aus Rice for Zinc Deficiency Tolerance Identified Through Association Analysis Using High-Density SNP Array
    Elsevier, 2018
    Co-Authors: Jaesung Lee, Matthias Wissuwa, Oscar B Zamora, Abdelbagi M Ismail
    Abstract:

    Zinc (Zn) deficiency is a major soil constraint limiting rice crop growth and yield, yet the genetic control of tolerance mechanisms is still poorly understood. Here, we presented promising loci and candidate genes conferring tolerance to Zn deficiency and identified through Association Analysis using a 365 K single nucleotide polymorphism (SNP) marker array in a diverse aus (semi-wild type rice) panel. Tolerant accessions exhibited higher growth rate with relatively rare stress symptoms. Two loci on chromosomes 7 and 9 were strongly associated with plant vigor under Zn deficiency at a peak-stress stage. Based on previous microarray data from the same experimental plots, we highlighted four candidate genes whose expressions were accompanied by significant genotype and/or environment effects under Zn deficiency. Network-gene ontology supported known tolerance mechanisms, such as ascorbic acid pathway, and also suggested the importance of photosynthesis genes to overcome Zn deficiency symptoms. Keywords: aus, genome-wide Association study, Zinc deficiency, ric