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https://www.readbyqxmd.com/read/27910927/novel-chemoimmunotherapeutic-strategy-for-hepatocellular-carcinoma-based-on-a-genome-wide-association-study
#1
Kaku Goto, Dorcas A Annan, Tomoko Morita, Wenwen Li, Ryosuke Muroyama, Yasuo Matsubara, Sayaka Ito, Ryo Nakagawa, Yasushi Tanoue, Masahisa Jinushi, Naoya Kato
Pharmacotherapeutic options are limited for hepatocellular carcinoma (HCC). Recently, we identified the anti-tumor ligand MHC class I polypeptide-related sequence A (MICA) gene as a susceptibility gene for hepatitis C virus-induced HCC in a genome-wide association study (GWAS). To prove the concept of HCC immunotherapy based on the results of a GWAS, in the present study, we searched for drugs that could restore MICA expression. A screen of the FDA-approved drug library identified the anti-cancer agent vorinostat as the strongest hit, suggesting histone deacetylase inhibitors (HDACis) as potent candidates...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905878/genomic-prediction-using-preselected-dna-variants-from-a-gwas-with-whole-genome-sequence-data-in-holstein-friesian-cattle
#2
Roel F Veerkamp, Aniek C Bouwman, Chris Schrooten, Mario P L Calus
BACKGROUND: Whole-genome sequence data is expected to capture genetic variation more completely than common genotyping panels. Our objective was to compare the proportion of variance explained and the accuracy of genomic prediction by using imputed sequence data or preselected SNPs from a genome-wide association study (GWAS) with imputed whole-genome sequence data. METHODS: Phenotypes were available for 5503 Holstein-Friesian bulls. Genotypes were imputed up to whole-genome sequence (13,789,029 segregating DNA variants) by using run 4 of the 1000 bull genomes project...
December 1, 2016: Genetics, Selection, Evolution: GSE
https://www.readbyqxmd.com/read/27903283/systematic-analysis-of-chromatin-interactions-at-disease-associated-loci-links-novel-candidate-genes-to-inflammatory-bowel-disease
#3
Claartje A Meddens, Magdalena Harakalova, Noortje A M van den Dungen, Hassan Foroughi Asl, Hemme J Hijma, Edwin P J G Cuppen, Johan L M Björkegren, Folkert W Asselbergs, Edward E S Nieuwenhuis, Michal Mokry
BACKGROUND: Genome-wide association studies (GWAS) have revealed many susceptibility loci for complex genetic diseases. For most loci, the causal genes have not been identified. Currently, the identification of candidate genes is predominantly based on genes that localize close to or within identified loci. We have recently shown that 92 of the 163 inflammatory bowel disease (IBD)-loci co-localize with non-coding DNA regulatory elements (DREs). Mutations in DREs can contribute to IBD pathogenesis through dysregulation of gene expression...
November 30, 2016: Genome Biology
https://www.readbyqxmd.com/read/27902805/genome-wide-association-mapping-reveals-novel-qtl-for-seedling-leaf-rust-resistance-in-a-worldwide-collection-of-winter-wheat
#4
Genqiao Li, Xiangyang Xu, Guihua Bai, Brett F Carver, Robert Hunger, J Michael Bonman, James Kolmer, Hongxu Dong
Leaf rust of wheat ( L.) is a major disease that causes significant yield losses worldwide. The short-lived nature of leaf rust resistance () genes necessitates a continuous search for novel sources of resistance. We performed a genome-wide association study (GWAS) on a panel of 1596 wheat accessions. The panel was evaluated for leaf rust reaction by testing with a bulk of Eriks. () isolates collected from multiple fields of Oklahoma in 2013 and two predominant races in the fields of Oklahoma in 2015. The panel was genotyped with a set of 5011 single-nucleotide polymorphism (SNP) markers...
November 2016: Plant Genome
https://www.readbyqxmd.com/read/27902795/genome-wide-association-study-identifies-candidate-loci-underlying-agronomic-traits-in-a-middle-american-diversity-panel-of-common-bean
#5
Samira Mafi Moghaddam, Sujan Mamidi, Juan M Osorno, Rian Lee, Mark Brick, James Kelly, Phillip Miklas, Carlos Urrea, Qijian Song, Perry Cregan, Jane Grimwood, Jeremy Schmutz, Phillip E McClean
Common bean ( L.) breeding programs aim to improve both agronomic and seed characteristics traits. However, the genetic architecture of the many traits that affect common bean production are not completely understood. Genome-wide association studies (GWAS) provide an experimental approach to identify genomic regions where important candidate genes are located. A panel of 280 modern bean genotypes from race Mesoamerica, referred to as the Middle American Diversity Panel (MDP), were grown in four US locations, and a GWAS using >150,000 single-nucleotide polymorphisms (SNPs) (minor allele frequency [MAF] ≥ 5%) was conducted for six agronomic traits...
November 2016: Plant Genome
https://www.readbyqxmd.com/read/27902791/genome-wide-association-mapping-of-leaf-rust-response-in-a-durum-wheat-worldwide-germplasm-collection
#6
Meriem Aoun, Matthew Breiland, M Kathryn Turner, Alexander Loladze, Shiaoman Chao, Steven S Xu, Karim Ammar, James A Anderson, James A Kolmer, Maricelis Acevedo
Leaf rust (caused by Erikss. []) is increasingly impacting durum wheat ( L. var. ) production with the recent appearance of races with virulence to widely grown cultivars in many durum producing areas worldwide. A highly virulent race on durum wheat was recently detected in Kansas. This race may spread to the northern Great Plains, where most of the US durum wheat is produced. The objective of this study was to identify sources of resistance to several races from the United States and Mexico at seedling stage in the greenhouse and at adult stage in field experiments...
November 2016: Plant Genome
https://www.readbyqxmd.com/read/27902751/exploration-of-a-polygenic-risk-score-for-alcohol-consumption-a-longitudinal-analysis-from-the-alspac-cohort
#7
Michelle Taylor, Andrew J Simpkin, Philip C Haycock, Frank Dudbridge, Luisa Zuccolo
BACKGROUND: Uncertainty remains about the true extent by which alcohol consumption causes a number of health outcomes. Genetic variants, or combinations of variants built into a polygenic risk score (PGRS), can be used in an instrumental variable framework to assess causality between a phenotype and disease outcome of interest, a method known as Mendelian randomisation (MR). We aimed to identify genetic variants involved in the aetiology of alcohol consumption, and develop a PGRS for alcohol...
2016: PloS One
https://www.readbyqxmd.com/read/27902686/genomic-characterization-of-metformin-hepatic-response
#8
Marcelo R Luizon, Walter L Eckalbar, Yao Wang, Stacy L Jones, Robin P Smith, Megan Laurance, Lawrence Lin, Paul J Gallins, Amy S Etheridge, Fred Wright, Yihui Zhou, Cliona Molony, Federico Innocenti, Sook Wah Yee, Kathleen M Giacomini, Nadav Ahituv
Metformin is used as a first-line therapy for type 2 diabetes (T2D) and prescribed for numerous other diseases. However, its mechanism of action in the liver has yet to be characterized in a systematic manner. To comprehensively identify genes and regulatory elements associated with metformin treatment, we carried out RNA-seq and ChIP-seq (H3K27ac, H3K27me3) on primary human hepatocytes from the same donor treated with vehicle control, metformin or metformin and compound C, an AMP-activated protein kinase (AMPK) inhibitor (allowing to identify AMPK-independent pathways)...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27901213/the-rs11191580-variant-of-the-nt5c2-gene-is-associated-with-schizophrenia-and-symptom-severity-in-a-south-chinese-han-population-evidence-from-gwas
#9
Zhen Li, Juan Jiang, Jianxiong Long, Weijun Ling, Guifeng Huang, Xiaojing Guo, Li Su
Objective: Recent genome-wide association studies have identified a significant relationship between the NT5C2 variant rs11191580 and schizophrenia (SCZ) in European populations. This study aimed to validate the association of rs11191580 polymorphism with SCZ risk in a South Chinese Han population. The relationship of this polymorphism with the severity of SCZ clinical symptoms was also explored. Methods: A case-control study was performed in 462 patients with SCZ and 598 healthy controls...
November 24, 2016: Revista Brasileira de Psiquiatria
https://www.readbyqxmd.com/read/27901114/genome-wide-diversity-and-association-mapping-for-capsaicinoids-and-fruit-weight-in-capsicum-annuum-l
#10
Padma Nimmakayala, Venkata L Abburi, Thangasamy Saminathan, Suresh B Alaparthi, Aldo Almeida, Brittany Davenport, Marjan Nadimi, Joshua Davidson, Krittika Tonapi, Lav Yadav, Sridhar Malkaram, Gopinath Vajja, Gerald Hankins, Robert Harris, Minkyu Park, Doil Choi, John Stommel, Umesh K Reddy
Accumulated capsaicinoid content and increased fruit size are traits resulting from Capsicum annuum domestication. In this study, we used a diverse collection of C. annuum to generate 66,960 SNPs using genotyping by sequencing. The study identified 1189 haplotypes containing 3413 SNPs. Length of individual linkage disequilibrium (LD) blocks varied along chromosomes, with regions of high and low LD interspersed with an average LD of 139 kb. Principal component analysis (PCA), Bayesian model based population structure analysis and an Euclidean tree built based on identity by state (IBS) indices revealed that the clustering pattern of diverse accessions are in agreement with capsaicin content (CA) and fruit weight (FW) classifications indicating the importance of these traits in shaping modern pepper genome...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900365/genome-sequencing-in-a-case-of-niemann-pick-type-c
#11
Max Dougherty, John Lazar, Jason C Klein, Karina Diaz, Theodore Gobillot, Eli Grunblatt, Nicholas Hasle, Daniel Lawrence, Megan Maurano, Maria Nelson, Gregory Olson, Sanjay Srivatsan, Jay Shendure, C Dirk Keene, Thomas Bird, Marshall S Horwitz, Desiree A Marshall
Adult-onset Niemann-Pick disease type C (NPC) is an infrequent presentation of a rare neurovisceral lysosomal lipid storage disorder caused by autosomal recessive mutations in NPC1 (∼95%) or NPC2 (∼5%). Our patient was diagnosed at age 33 when he presented with a 10-yr history of difficulties in judgment, concentration, speech, and coordination. A history of transient neonatal jaundice and splenomegaly with bone marrow biopsy suggesting a lipid storage disorder pointed to NPC; biochemical ("variant" level cholesterol esterification) and ultrastructural studies in adulthood confirmed the diagnosis...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27899670/the-new-nhgri-ebi-catalog-of-published-genome-wide-association-studies-gwas-catalog
#12
Jacqueline MacArthur, Emily Bowler, Maria Cerezo, Laurent Gil, Peggy Hall, Emma Hastings, Heather Junkins, Aoife McMahon, Annalisa Milano, Joannella Morales, Zoe May Pendlington, Danielle Welter, Tony Burdett, Lucia Hindorff, Paul Flicek, Fiona Cunningham, Helen Parkinson
The NHGRI-EBI GWAS Catalog has provided data from published genome-wide association studies since 2008. In 2015, the database was redesigned and relocated to EMBL-EBI. The new infrastructure includes a new graphical user interface (www.ebi.ac.uk/gwas/), ontology supported search functionality and an improved curation interface. These developments have improved the data release frequency by increasing automation of curation and providing scaling improvements. The range of available Catalog data has also been extended with structured ancestry and recruitment information added for all studies...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899403/meta-analysis-of-genome-wide-association-studies-for-abdominal-aortic-aneurysm-identifies-four-new-disease-specific-risk-loci
#13
Gregory T Jones, Gerard Tromp, Helena Kuivaniemi, Solveig Gretarsdottir, Annette F Baas, Betti Giusti, Ewa Strauss, Femke N van 't Hof, Thomas Webb, Robert Erdman, Marylyn D Ritchie, James R Elmore, Anurag Verma, Sarah Pendergrass, Iftikhar J Kullo, Zi Ye, Peggy L Peissig, Omri Gottesman, Shefali S Verma, Jennifer Malinowski, Laura J Rasmussen-Torvik, Kenneth Borthwick, Diane T Smelser, David R Crosslin, Mariza de Andrade, Evan J Ryer, Catherine A McCarty, Erwin P Bottinger, Jennifer A Pacheco, Dana C Crawford, David S Carrell, Glenn S Gerhard, David P Franklin, David J Carey, Victoria L Phillips, Michael J Williams, Wenhua Wei, Ross Blair, Andrew A Hill, Thodur M Vasudevan, David R Lewis, Ian A Thomson, Jo Krysa, Geraldine B Hill, Justin Roake, Tony R Merriman, Grzegorz Oszkinis, Silvia Galora, Claudia Saracini, Rosanna Abbate, Raffaele Pulli, Carlo Pratesi, Athanasios Saratzis, Anna Verissimo, Suzannah J Bumpstead, Stephen A Badger, Rachel E Clough, Gillian W Cockerill, Hany Hafez, D J Scott, T S Futers, Simon P Romaine, Katherine Bridge, Kathryn J Griffin, Marc A Bailey, Alberto Smith, Matt M Thompson, Frank van Bockxmeer, Stefan E Matthiasson, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Jan D Blankensteijn, Joep A Teijink, Cisca Wijmenga, Jacqueline de Graaf, Lambertus A Kiemeney, Jes S Lindholt, Anne E Hughes, Declan T Bradley, Kathleen Stirrups, Jonathan Golledge, Paul E Norman, Janet T Powell, Steve E Humphries, Stephen E Hamby, Alison H Goodall, Christopher P Nelson, Natzi Sakalihasan, Audrey Courtois, Robert E Ferrell, Per Eriksson, Lasse Folkersen, Anders Franco-Cereceda, John D Eicher, Andrew D Johnson, Christer Betsholtz, Arno Ruusalepp, Oscar Franzén, Eric Schadt, Johan L Björkegren, Leonard Lipovich, Anne M Drolet, Eric Verhoeven, Clark J Zeebregts, Robert H Geelkerken, Marc R van Sambeek, Steven M van Sterkenburg, Jean-Paul P de Vries, Kari Stefansson, John R Thompson, Paul I de Bakker, Panos Deloukas, Robert D Sayers, Seamus Harrison, Andre M van Rij, Nilesh J Samani, Matthew J Bown
RATIONALE: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. OBJECTIVE: To identify additional AAA risk loci using data from all available genome-wide association studies (GWAS). METHODS AND RESULTS: Through a meta-analysis of 6 GWAS datasets and a validation study totalling 10,204 cases and 107,766 controls we identified 4 new AAA risk loci: 1q32...
November 29, 2016: Circulation Research
https://www.readbyqxmd.com/read/27899376/gwas-of-clinically-defined-gout-and-subtypes-identifies-multiple-susceptibility-loci-that-include-urate-transporter-genes
#14
Akiyoshi Nakayama, Hirofumi Nakaoka, Ken Yamamoto, Masayuki Sakiyama, Amara Shaukat, Yu Toyoda, Yukinori Okada, Yoichiro Kamatani, Takahiro Nakamura, Tappei Takada, Katsuhisa Inoue, Tomoya Yasujima, Hiroaki Yuasa, Yuko Shirahama, Hiroshi Nakashima, Seiko Shimizu, Toshihide Higashino, Yusuke Kawamura, Hiraku Ogata, Makoto Kawaguchi, Yasuyuki Ohkawa, Inaho Danjoh, Atsumi Tokumasu, Keiko Ooyama, Toshimitsu Ito, Takaaki Kondo, Kenji Wakai, Blanka Stiburkova, Karel Pavelka, Lisa K Stamp, Nicola Dalbeth, Yutaka Sakurai, Hiroshi Suzuki, Makoto Hosoyamada, Shin Fujimori, Takashi Yokoo, Tatsuo Hosoya, Ituro Inoue, Atsushi Takahashi, Michiaki Kubo, Hiroshi Ooyama, Toru Shimizu, Kimiyoshi Ichida, Nariyoshi Shinomiya, Tony R Merriman, Hirotaka Matsuo
OBJECTIVE: A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. METHODS: Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zealand Polynesian samples was done to further validate the loci identified in this study...
November 29, 2016: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/27899190/genetic-changes-associated-with-testicular-cancer-susceptibility
#15
REVIEW
Louise C Pyle, Katherine L Nathanson
Testicular germ cell tumor (TGCT) is a highly heritable cancer primarily affecting young white men. Genome-wide association studies (GWAS) have been particularly effective in identifying multiple common variants with strong contribution to TGCT risk. These loci identified through association studies have implicated multiple genes as associated with TGCT predisposition, many of which are unique among cancer types, and regulate processes such as pluripotency, sex specification, and microtubule assembly. Together these biologically plausible genes converge on pathways involved in male germ cell development and maturation, and suggest that perturbation of them confers susceptibility to TGCT, as a developmental defect of germ cell differentiation...
October 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/27899188/familial-prostate-cancer
#16
Veda N Giri, Jennifer L Beebe-Dimmer
Prostate cancer is the most commonly diagnosed cancer among men in the United States as well as most Western countries. A significant proportion of men report having a positive family history of prostate cancer in a first-degree relative (father, brother, son), which is important in that family history is one of the only established risk factors for the disease and plays a role in decision-making for prostate cancer screening. Familial aggregation of prostate cancer is considered a surrogate marker of genetic susceptibility to developing the disease, but shared environment cannot be excluded as an explanation for clustering of cases among family members...
October 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/27898967/genomewide-association-analysis-of-growth-traits-in-charolais-beef-cattle
#17
F J Jahuey-Martínez, G M Parra-Bracamonte, A M Sifuentes-Rincón, J C Martínez-González, C Gondro, C A García-Pérez, L A López-Bustamante
The objective of this study was to perform a genomewide association study (GWAS) for growth traits in Charolais beef cattle and to identify SNP markers and genes associated with these traits. Our study included 855 animals genotyped using 76,883 SNP from the GeneSeek Genomic Profiler Bovine HD panel. The examined phenotypic data included birth, weaning, and yearling weights as well as pre- and postweaning ADG. After quality control, 68,337 SNP and 823 animals were retained in the analysis. The association analysis was performed using the principal components method via the egscore function of the GenABEL version 1...
November 2016: Journal of Animal Science
https://www.readbyqxmd.com/read/27898829/gapit-version-2-an-enhanced-integrated-tool-for-genomic-association-and-prediction
#18
You Tang, Xiaolei Liu, Jiabo Wang, Meng Li, Qishan Wang, Feng Tian, Zhongbin Su, Yuchun Pan, Di Liu, Alexander E Lipka, Edward S Buckler, Zhiwu Zhang
Most human diseases and agriculturally important traits are complex. Dissecting their genetic architecture requires continued development of innovative and powerful statistical methods. Corresponding advances in computing tools are critical to efficiently use these statistical innovations and to enhance and accelerate biomedical and agricultural research and applications. The genome association and prediction integrated tool (GAPIT) was first released in 2012 and became widely used for genome-wide association studies (GWAS) and genomic prediction...
July 2016: Plant Genome
https://www.readbyqxmd.com/read/27898828/population-structure-in-the-model-grass-is-highly-correlated-with-flowering-differences-across-broad-geographic-areas
#19
Ludmila Tyler, Scott J Lee, Nelson D Young, Gregory A DeIulio, Elena Benavente, Michael Reagon, Jessica Sysopha, Riccardo M Baldini, Angelo Troìa, Samuel P Hazen, Ana L Caicedo
The small, annual grass (L.) Beauv., a close relative of wheat ( L.) and barley ( L.), is a powerful model system for cereals and bioenergy grasses. Genome-wide association studies (GWAS) of natural variation can elucidate the genetic basis of complex traits but have been so far limited in by the lack of large numbers of well-characterized and sufficiently diverse accessions. Here, we report on genotyping-by-sequencing (GBS) of 84 , seven , and three accessions with diverse geographic origins including Albania, Armenia, Georgia, Italy, Spain, and Turkey...
July 2016: Plant Genome
https://www.readbyqxmd.com/read/27898824/genome-wide-association-study-of-brown-stem-rot-resistance-in-soybean-across-multiple-populations
#20
Keith Rincker, Alexander E Lipka, Brian W Diers
Genetic resistance to brown stem rot (BSR) of soybean [ (L.) Merr.], caused by (Allington & D.W. Chamb.) T.C. Harr. & McNew, has been identified and mapped with biparental populations. Although nearly 400 accessions have been identified with BSR resistance, this trait has been mapped in only 12 sources, and just two, PI84946-2 and PI88788, have been used to develop BSR resistant cultivars. Thus, there is a serious need to improve our knowledge of the genetic basis of BSR resistance in soybean so that resistance genes in cultivars can be diversified and markers close to resistance genes can be identified and used in marker-assisted selection (MAS)...
July 2016: Plant Genome
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