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https://www.readbyqxmd.com/read/28346484/a-neighborhood-wide-association-study-nwas-example-of-prostate-cancer-aggressiveness
#1
Shannon M Lynch, Nandita Mitra, Michelle Ross, Craig Newcomb, Karl Dailey, Tara Jackson, Charnita M Zeigler-Johnson, Harold Riethman, Charles C Branas, Timothy R Rebbeck
PURPOSE: Cancer results from complex interactions of multiple variables at the biologic, individual, and social levels. Compared to other levels, social effects that occur geospatially in neighborhoods are not as well-studied, and empiric methods to assess these effects are limited. We propose a novel Neighborhood-Wide Association Study(NWAS), analogous to genome-wide association studies(GWAS), that utilizes high-dimensional computing approaches from biology to comprehensively and empirically identify neighborhood factors associated with disease...
2017: PloS One
https://www.readbyqxmd.com/read/28346479/rare-variants-in-fox-1-homolog-a-rbfox1-are-associated-with-lower-blood-pressure
#2
Karen Y He, Heming Wang, Brian E Cade, Priyanka Nandakumar, Ayush Giri, Erin B Ware, Jeffrey Haessler, Jingjing Liang, Jennifer A Smith, Nora Franceschini, Thu H Le, Charles Kooperberg, Todd L Edwards, Sharon L R Kardia, Xihong Lin, Aravinda Chakravarti, Susan Redline, Xiaofeng Zhu
Many large genome-wide association studies (GWAS) have identified common blood pressure (BP) variants. However, most of the identified BP variants do not overlap with the linkage evidence observed from family studies. We thus hypothesize that multiple rare variants contribute to the observed linkage evidence. We performed linkage analysis using 517 individuals in 130 European families from the Cleveland Family Study (CFS) who have been genotyped on the Illumina OmniExpress Exome array. The largest linkage peak was observed on chromosome 16p13 (MLOD = 2...
March 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28346443/genome-wide-association-study-of-glioma-subtypes-identifies-specific-differences-in-genetic-susceptibility-to-glioblastoma-and-non-glioblastoma-tumors
#3
Beatrice S Melin, Jill S Barnholtz-Sloan, Margaret R Wrensch, Christoffer Johansen, Dora Il'yasova, Ben Kinnersley, Quinn T Ostrom, Karim Labreche, Yanwen Chen, Georgina Armstrong, Yanhong Liu, Jeanette E Eckel-Passow, Paul A Decker, Marianne Labussière, Ahmed Idbaih, Khe Hoang-Xuan, Anna-Luisa Di Stefano, Karima Mokhtari, Jean-Yves Delattre, Peter Broderick, Pilar Galan, Konstantinos Gousias, Johannes Schramm, Minouk J Schoemaker, Sarah J Fleming, Stefan Herms, Stefanie Heilmann, Markus M Nöthen, Heinz-Erich Wichmann, Stefan Schreiber, Anthony Swerdlow, Mark Lathrop, Matthias Simon, Marc Sanson, Ulrika Andersson, Preetha Rajaraman, Stephen Chanock, Martha Linet, Zhaoming Wang, Meredith Yeager, John K Wiencke, Helen Hansen, Lucie McCoy, Terri Rice, Matthew L Kosel, Hugues Sicotte, Christopher I Amos, Jonine L Bernstein, Faith Davis, Dan Lachance, Ching Lau, Ryan T Merrell, Joellen Shildkraut, Francis Ali-Osman, Siegal Sadetzki, Michael Scheurer, Sanjay Shete, Rose K Lai, Elizabeth B Claus, Sara H Olson, Robert B Jenkins, Richard S Houlston, Melissa L Bondy
Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 × 10(-9), odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 × 10(-10), OR = 1.24), 16p13.3 (rs2562152; P = 1.93 × 10(-8), OR = 1.21), 16q12...
March 27, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28344127/replicated-association-between-the-european-gwas-locus-rs10503253-at-csmd1-and-schizophrenia-in-asian-population
#4
Weiqing Liu, Fang Liu, Xiufeng Xu, Yan Bai
Schizophrenia is one of the most severe mental disorders with significant heritability. Recent genetic association studies including genome-wide association studies (GWAS) have identified multiple common variants conferring risk of schizophrenia. An intronic SNP within CSMD1, rs10503253, is one of the top risk SNPs for schizophrenia in Europeans discovered through large GWAS. However, whether rs10503253 is also a risk SNP for schizophrenia in other populations, such as Asians, is still unknown. To answer this question, we examined the association of rs10503253 with schizophrenia in a total of 7,514 schizophrenia patients, 9,058 healthy controls and 1,115 nuclear families originated from Asia using a meta-analytic approach...
March 23, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28341552/identification-of-a-molecular-signaling-gene-gene-regulatory-network-between-gwas-susceptibility-genes-adtrp-and-mia3-tango1-for-coronary-artery-disease
#5
Chunyan Luo, Fan Wang, Xiang Ren, Tie Ke, Chengqi Xu, Bo Tang, Subo Qin, Yufeng Yao, Qiuyun Chen, Qing Kenneth Wang
Coronary artery disease (CAD) is the leading cause of death worldwide. GWAS have identified >50 genomic loci for CAD, including ADTRP and MIA3/TANGO1. However, it is important to determine whether the GWAS genes form a molecular network. In this study, we have uncovered a novel molecular network between ADTRP and MIA3/TANGO1 for the pathogenesis of CAD. We showed that knockdown of ADTRP expression markedly down-regulated expression of MIA3/TANGO1. Mechanistically, ADTRP positively regulates expression of PIK3R3 encoding the regulatory subunit 3 of PI3K, which leads to activation of AKT, resulting in up-regulation of MIA3/TANGO1...
March 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28339749/multi-generational-genome-wide-association-studies-identify-chromosomal-regions-associated-with-ascites-phenotype
#6
K J Tarrant, S Dey, R Kinney, N B Anthony, D D Rhoads
Ascites is a multi-faceted disease commonly observed in fast growing broilers, which is initiated when the body is insufficiently oxygenated. A series of events follow, including an increase in pulmonary artery pressure, right ventricle hypertrophy, and accumulation of fluid in the abdominal cavity and pericardium. Advances in management practices along with improved selection programs have decreased ascites incidence in modern broilers. However, ascites syndrome remains an economically important disease throughout the world, causing estimated losses of $100 million per year...
February 21, 2017: Poultry Science
https://www.readbyqxmd.com/read/28339748/genotype-based-gene-signature-of-glioma-risk
#7
Yen-Tsung Huang, Yi Zhang, Zhijin Wu, Dominique S Michaud
Background.: Glioma accounts for 80% of malignant brain tumors, but its etiologic determinants remain elusive. Despite genetic susceptibility loci identified by genome-wide association study (GWAS), the agnostic approach leaves open the possibility that other susceptibility genes remain to be discovered. Here we conduct a gene-centric integrative GWAS (iGWAS) of glioma risk that combines transcriptomics and genetics. Methods.: We synthesized a brain transcriptomics dataset (n = 354), a GWAS dataset (n = 4203), and an advanced glioma tumor transcriptomic dataset (n = 483) to conduct an iGWAS...
February 22, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28339549/further-investigation-of-a-quantitative-trait-locus-for-ascites-on-chromosome-9-in-broiler-chicken-lines
#8
Shatovisha Dey, Sriram Krishna, Nicholas B Anthony, Douglas D Rhoads
Previously, we reported a genome wide association study (GWAS) that had shown association of a region between 11.8 and 13.6 Mbp on chromosome 9 with ascites phenotype in broilers. We had used microsatellite loci to demonstrate an association of particular genotypes for this region with ascites in experimental ascites lines and commercial broiler breeder lines. We identified two potential candidate genes, AGTR1 and UTS2D, within that chromosomal region for mediating the quantitative effect. We have now extended our analysis using SNPs for these genes to assess association with resistance or susceptibility to ascites in these same broiler lines...
October 10, 2016: Poultry Science
https://www.readbyqxmd.com/read/28338987/gamma-glutamyltransferase-levels-prediabetes-and-type-2-diabetes-a-mendelian-randomization-study
#9
Jana Nano, Taulant Muka, Symen Ligthart, Albert Hofman, Sarwa Darwish Murad, Harry LA Janssen, Oscar H Franco, Abbas Dehghan
Background: High levels of serum gamma-glutamyltransferase (GGT) are associated with increased risk of prediabetes and type 2 diabetes in observational studies. It is unclear whether this relationship is causal, arises from residual confounding or is a consequence of reverse causation. Methods: We used data from a prospective population-based cohort study, compromising 8611 individuals without diabetes at baseline. Cox proportional hazard models were used to study the association between serum GGT levels and incident prediabetes and diabetes...
March 13, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28338805/deciphering-the-genetic-control-of-fruit-texture-in-apple-by-multiple-family-based-analysis-and-genome-wide-association
#10
Mario Di Guardo, Marco C A M Bink, Walter Guerra, Thomas Letschka, Lidia Lozano, Nicola Busatto, Lara Poles, Alice Tadiello, Luca Bianco, Richard G F Visser, Eric van de Weg, Fabrizio Costa
Fruit texture is a complex feature composed of mechanical and acoustic properties relying on the modifications occurring in the cell wall throughout fruit development and ripening. Apple is characterized by a large variation in fruit texture behavior that directly impacts both the consumer's appreciation and post-harvest performance. To decipher the genetic control of fruit texture comprehensively, two complementing quantitative trait locus (QTL) mapping approaches were employed. The first was represented by a pedigree-based analysis (PBA) carried out on six full-sib pedigreed families, while the second was a genome-wide association study (GWAS) performed on a collection of 233 apple accessions...
February 24, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28338774/pleiotropy-robust-mendelian-randomization
#11
Hans van Kippersluis, Cornelius A Rietveld
Background: The potential of Mendelian randomization studies is rapidly expanding due to: (i) the growing power of genome-wide association study (GWAS) meta-analyses to detect genetic variants associated with several exposures; and (ii) the increasing availability of these genetic variants in large-scale surveys. However, without a proper biological understanding of the pleiotropic working of genetic variants, a fundamental assumption of Mendelian randomization (the exclusion restriction) can always be contested...
February 22, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28335481/genetic-variants-contributing-to-colistin-cytotoxicity-identification-of-tgif1-and-hoxd10-using-a-population-genomics-approach
#12
Michael T Eadon, Ronald J Hause, Amy L Stark, Ying-Hua Cheng, Heather E Wheeler, Kimberly S Burgess, Eric A Benson, Patrick N Cunningham, Robert L Bacallao, Pierre C Dagher, Todd C Skaar, M Eileen Dolan
Colistin sulfate (polymixin E) is an antibiotic prescribed with increasing frequency for severe Gram-negative bacterial infections. As nephrotoxicity is a common side effect, the discovery of pharmacogenomic markers associated with toxicity would benefit the utility of this drug. Our objective was to identify genetic markers of colistin cytotoxicity that were also associated with expression of key proteins using an unbiased, whole genome approach and further evaluate the functional significance in renal cell lines...
March 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28334983/gwas-linked-ppargc1a-variant-in-asian-patients-with-essential-tremor
#13
Bin Xiao, Xiao Deng, Ebonne Yu-Lin Ng, Murni Tio, Kumar M Prakash, Wing Lok Au, Louis Tan, Yi Zhao, Eng-King Tan
No abstract text is available yet for this article.
February 20, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334950/downstream-targets-of-gwas-detected-genes-for-breast-lung-and-prostate-and-colon-cancer-converge-to-g1-s-transition-pathway
#14
Olga Y Gorlova, Eugene I Demidenko, Christopher I Amos, Ivan P Gorlov
Genome-wide association studies (GWASs) identified over 500 single nucleotide polymorphisms (SNPs) influencing cancer risk. It is logical to expect the cancer-associated genes to cluster in pathways directly involved in carcinogenesis, e.g. cell cycle. Nevertheless, analyses of the GWAS-detected cancer risk genes usually show no or weak enrichment by known cancer genes.We hypothesized that GWAS-detected cancer risk-associated genes function as upstream regulators of the genes directly involved in carcinogenesis...
March 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334935/genome-wide-association-study-of-iron-traits-and-relation-to-diabetes-in-the-hispanic-community-health-study-study-of-latinos-hchs-sol-potential-genomic-intersection-of-iron-and-glucose-regulation
#15
Laura M Raffield, Tin Louie, Tamar Sofer, Deepti Jain, Eli Ipp, Kent D Taylor, George J Papanicolaou, Larissa Avilés-Santa, Leslie A Lange, Cathy C Laurie, Matthew P Conomos, Timothy A Thornton, Yii-Der Ida Chen, Qibin Qi, Scott Cotler, Bharat Thyagarajan, Neil Schneiderman, Jerome I Rotter, Alex P Reiner, Henry J Lin
Genetic variants contribute to normal variation of iron-related traits and may also cause clinical syndromes of iron deficiency or excess. Iron overload and deficiency can adversely affect human health. For example, elevated iron storage is associated with increased diabetes risk, although mechanisms are still being investigated. We conducted the first genome-wide association study (GWAS) of serum iron, total iron binding capacity (TIBC), transferrin saturation, and ferritin in a Hispanic/Latino cohort, the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; >12,000 participants) and also assessed the generalization of previously known loci to this population...
March 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334899/association-analyses-of-east-asian-individuals-and-trans-ancestry-analyses-with-european-individuals-reveal-new-loci-associated-with-cholesterol-and-triglyceride-levels
#16
Cassandra N Spracklen, Peng Chen, Young Jin Kim, Xu Wang, Hui Cai, Shengxu Li, Jirong Long, Ying Wu, Ya Xing Wang, Fumihiko Takeuchi, Jer-Yuarn Wu, Keum-Ji Jung, Cheng Hu, Koichi Akiyama, Yonghong Zhang, Sanghoon Moon, Todd A Johnson, Huaixing Li, Rajkumar Dorajoo, Meian He, Maren E Cannon, Tamara S Roman, Elias Salfati, Keng-Hung Lin, Xiuqing Guo, Wayne H H Sheu, Devin Absher, Linda S Adair, Themistocles L Assimes, Tin Aung, Qiuyin Cai, Li-Ching Chang, Chien-Hsiun Chen, Li-Hsin Chien, Lee-Ming Chuang, Shu-Chun Chuang, Shufa Du, Qiao Fan, Cathy S J Fann, Alan B Feranil, Yechiel Friedlander, Penny Gordon-Larsen, Dongfeng Gu, Lixuan Gui, Zhirong Guo, Chew-Kiat Heng, James Hixson, Xuhong Hou, Chao Agnes Hsiung, Yao Hu, Mi Yeong Hwang, Chii-Min Hwu, Masato Isono, Jyh-Ming Jimmy Juang, Chiea-Chuen Khor, Yun Kyoung Kim, Woon-Puay Koh, Michiaki Kubo, I-Te Lee, Sun-Ju Lee, Wen-Jane Lee, Kae-Woei Liang, Blanche Lim, Sing-Hui Lim, Jianjun Liu, Toru Nabika, Wen-Harn Pan, Hao Peng, Thomas Quertermous, Charumathi Sabanayagam, Kevin Sandow, Jinxiu Shi, Liang Sun, Pok Chien Tan, Shu-Pei Tan, Kent D Taylor, Yik-Ying Teo, Sue-Anne Toh, Tatsuhiko Tsunoda, Rob M van Dam, Aili Wang, Feijie Wang, Jie Wang, Wen Bin Wei, Yong-Bing Xiang, Jie Yao, Jian-Min Yuan, Rong Zhang, Wanting Zhao, Yii-Der Ida Chen, Stephen S Rich, Jerome I Rotter, Tzung-Dau Wang, Tangchun Wu, Xu Lin, Bok-Ghee Han, Toshihiro Tanaka, Yoon Shin Cho, Tomohiro Katsuya, Weiping Jia, Sun-Ha Jee, Yuan-Tsong Chen, Norihiro Kato, Jost B Jonas, Ching-Yu Cheng, Xiao-Ou Shu, Jiang He, Wei Zheng, Tien-Yin Wong, Wei Huang, Bong-Jo Kim, E-Shyong Tai, Karen L Mohlke, Xueling Sim
Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan...
February 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334860/genetic-regulation-of-gene-expression-in-the-epileptic-human-hippocampus
#17
Nasir Mirza, Richard Appleton, Sasha Burn, Daniel du Plessis, Roderick Duncan, Jibril Osman Farah, Bjarke Feenstra, Anders Hviid, Vivek Josan, Rajiv Mohanraj, Arif Shukralla, Graeme J Sills, Anthony G Marson, Munir Pirmohamed
Epilepsy is a serious and common neurological disorder. Expression quantitative loci (eQTL) analysis is a vital aid for the identification and interpretation of disease-risk loci. Many eQTLs operate in a tissue- and condition-specific manner. We have performed the first genome-wide cis-eQTL analysis of human hippocampal tissue to include not only normal (n = 22) but also epileptic (n = 22) samples. We demonstrate that disease-associated variants from an epilepsy GWAS meta-analysis and a febrile seizures (FS) GWAS are significantly more enriched with epilepsy-eQTLs than with normal hippocampal eQTLs from two larger independent published studies...
March 3, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334830/predicting-the-impact-of-non-coding-variants-on-dna-methylation
#18
Haoyang Zeng, David K Gifford
DNA methylation plays a crucial role in the establishment of tissue-specific gene expression and the regulation of key biological processes. However, our present inability to predict the effect of genome sequence variation on DNA methylation precludes a comprehensive assessment of the consequences of non-coding variation. We introduce CpGenie, a sequence-based framework that learns a regulatory code of DNA methylation using a deep convolutional neural network and uses this network to predict the impact of sequence variation on proximal CpG site DNA methylation...
March 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334792/gwas-identifies-population-specific-new-regulatory-variants-in-fut6-associated-with-plasma-b12-concentrations-in-indians
#19
Suraj S Nongmaithem, Charudatta V Joglekar, Ghattu V Krishnaveni, Sirazul A Sahariah, Meraj Ahmad, Swetha Ramachandran, Meera Gandhi, Harsha Chopra, Anand Pandit, Ramesh D Potdar, Caroline Hd Fall, Chittaranjan S Yajnik, Giriraj R Chandak
Vitamin B12 is an important cofactor in one-carbon metabolism whose dysregulation is associated with various clinical conditions. Indians have a high prevalence of B12 deficiency but little is known about the genetic determinants of circulating B12 concentrations in Indians. We performed a genome-wide association study in 1001 healthy participants in the Pune Maternal Nutrition Study (PMNS), replication studies in 3418 individuals from other Indian cohorts and by meta-analysis identified new variants, rs3760775 (p = 1...
February 27, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334615/the-ncam1-gene-set-is-linked-to-depressive-symptoms-and-their-brain-structural-correlates-in-healthy-individuals
#20
Jana Petrovska, David Coynel, Matthias Fastenrath, Annette Milnik, Bianca Auschra, Tobias Egli, Leo Gschwind, Francina Hartmann, Eva Loos, Klara Sifalakis, Christian Vogler, Dominique J-F de Quervain, Andreas Papassotiropoulos, Angela Heck
Depressive symptoms exist on a continuum, the far end of which is found in depressive disorders. Utilizing the continuous spectrum of depressive symptoms may therefore contribute to the understanding of the biological underpinnings of depression. Gene set enrichment analysis (GSEA) is an important tool for the identification of gene groups linked to complex traits, and was applied in the present study on genome-wide association study (GWAS) data of depression scores and their brain-level structural correlates in healthy young individuals...
March 6, 2017: Journal of Psychiatric Research
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