scholarly journals Prostate cancer genomics by high-throughput technologies: genome-wide association study and sequencing analysis

2013 ◽  
Vol 20 (4) ◽  
pp. R171-R181 ◽  
Author(s):  
Hidewaki Nakagawa
Keyword(s):  
Prostate Cancer ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Genome Wide Association Study ◽  
Cancer Genomics ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Sequencing Analysis ◽  
Genome Wide

Prostate cancer (PC) is the most common malignancy in males. It is evident that genetic factors at both germline and somatic levels play critical roles in prostate carcinogenesis. Recently, genome-wide association studies (GWAS) by high-throughput genotyping technology have identified more than 70 germline variants of various genes or chromosome loci that are significantly associated with PC susceptibility. They include multiple 8q24 loci, prostate-specific genes, and metabolism-related genes. Somatic alterations in PC genomes have been explored by high-throughput sequencing technologies such as whole-genome sequencing and RNA sequencing, which have identified a variety of androgen-responsive events and fusion transcripts represented by E26 transformation-specific (ETS) gene fusions. Recent innovations in high-throughput genomic technologies have enabled us to analyze PC genomics more comprehensively, more precisely, and on a larger scale in multiple ethnic groups to increase our understanding of PC genomics and biology in germline and somatic studies, which can ultimately lead to personalized medicine for PC diagnosis, prevention, and therapy. However, these data indicate that the PC genome is more complex and heterogeneous than we expected from GWAS and sequencing analyses.

scholarly journals 12 new susceptibility loci for prostate cancer identified by genome-wide association study in Japanese population

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Ryo Takata ◽  
Atsushi Takahashi ◽  
Masashi Fujita ◽  
Yukihide Momozawa ◽  
Edward J. Saunders ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Japanese Population ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
European Population ◽  
Genome Wide Association ◽  
High Risk Population ◽  
Genome Wide Association Studies ◽  
Susceptibility Loci ◽  
Genome Wide

Abstract Genome-wide association studies (GWAS) have identified ~170 genetic loci associated with prostate cancer (PCa) risk, but most of them were identified in European populations. We here performed a GWAS and replication study using a large Japanese cohort (9,906 cases and 83,943 male controls) to identify novel susceptibility loci associated with PCa risk. We found 12 novel loci for PCa including rs1125927 (TMEM17, P = 3.95 × 10−16), rs73862213 (GATA2, P = 5.87 × 10−23), rs77911174 (ZMIZ1, P = 5.28 × 10−20), and rs138708 (SUN2, P = 1.13 × 10−15), seven of which had crucially low minor allele frequency in European population. Furthermore, we stratified the polygenic risk for Japanese PCa patients by using 82 SNPs, which were significantly associated with Japanese PCa risk in our study, and found that early onset cases and cases with family history of PCa were enriched in the genetically high-risk population. Our study provides important insight into genetic mechanisms of PCa and facilitates PCa risk stratification in Japanese population.

scholarly journals Prostate cancer genomics, biology, and risk assessment through genome-wide association studies

2012 ◽  
Vol 103 (4) ◽  
pp. 607-613 ◽  
Author(s):  
Hidewaki Nakagawa ◽  
Shusuke Akamatsu ◽  
Ryo Takata ◽  
Atsushi Takahashi ◽  
Michiaki Kubo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Assessment ◽  
Cancer Genomics ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals Human Genomic Loci Important in Common Infectious Diseases: Role of High-Throughput Sequencing and Genome-Wide Association Studies

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Gerald Mboowa ◽  
Ivan Sserwadda ◽  
Marion Amujal ◽  
Norah Namatovu
Keyword(s):  
Infectious Diseases ◽  
Positive Selection ◽  
High Throughput ◽  
Large Scale ◽  
High Throughput Sequencing ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Host Pathogen

HIV/AIDS, tuberculosis (TB), and malaria are 3 major global public health threats that undermine development in many resource-poor settings. Recently, the notion that positive selection during epidemics or longer periods of exposure to common infectious diseases may have had a major effect in modifying the constitution of the human genome is being interrogated at a large scale in many populations around the world. This positive selection from infectious diseases increases power to detect associations in genome-wide association studies (GWASs). High-throughput sequencing (HTS) has transformed both the management of infectious diseases and continues to enable large-scale functional characterization of host resistance/susceptibility alleles and loci; a paradigm shift from single candidate gene studies. Application of genome sequencing technologies and genomics has enabled us to interrogate the host-pathogen interface for improving human health. Human populations are constantly locked in evolutionary arms races with pathogens; therefore, identification of common infectious disease-associated genomic variants/markers is important in therapeutic, vaccine development, and screening susceptible individuals in a population. This review describes a range of host-pathogen genomic loci that have been associated with disease susceptibility and resistant patterns in the era of HTS. We further highlight potential opportunities for these genetic markers.

scholarly journals Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Daniel L. McCartney ◽  
Josine L. Min ◽  
Rebecca C. Richmond ◽  
Ake T. Lu ◽  
Maria K. Sobczyk ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Genome Wide Association ◽  
Biological Aging ◽  
Genome Wide Association Studies ◽  
Genetic Loci ◽  
Biomarkers Of Aging ◽  
Genome Wide ◽  
Shared Genetic

Abstract Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

scholarly journals Functional annotation of risk loci identified through genome-wide association studies for prostate cancer

The Prostate ◽  
2010 ◽  
Vol 71 (9) ◽  
pp. 955-963 ◽  
Author(s):  
Yizhen Lu ◽  
Zheng Zhang ◽  
Hongjie Yu ◽  
S. Lily Zheng ◽  
William B. Isaacs ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Functional Annotation ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals Heritability and genome-wide association study of diffusing capacity of the lung

2018 ◽  
Author(s):  
Natalie Terzikhan ◽  
Fangui Sun ◽  
Fien M. Verhamme ◽  
Hieab H.H. Adams ◽  
Daan Loth ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Considerable Proportion ◽  
Genome Wide Association Studies ◽  
Diffusing Capacity ◽  
Human Lung Tissue ◽  
Alveolar Volume ◽  
Genome Wide

AbstractBackgroundAlthough several genome wide association studies (GWAS) have investigated the genetics of pulmonary ventilatory function, little is known about the genetic factors that influence gas exchange.AimTo investigate the heritability of, and genetic variants associated with the diffusing capacity of the lung.MethodsGWAS was performed on diffusing capacity, measured by carbon monoxide uptake (DLCO) and per alveolar volume (DLCO/VA) using the single-breath technique, in 8,372 individuals from two population-based cohort studies, the Rotterdam Study and the Framingham Heart Study. Heritability was estimated in related (n=6,246) and unrelated (n=3,286) individuals.ResultsHeritability of DLCO and DLCO/VA ranged between 23% and 28% in unrelated individuals and between 45% and 49% in related individuals. Meta-analysis identified a genetic variant in GPR126 that is significantly associated with DLCO/VA. Gene expression analysis of GPR126 in human lung tissue revealed a decreased expression in patients with COPD and subjects with decreased DLCO/VA.ConclusionDLCO and DLCO/VA are heritable traits, with a considerable proportion of variance explained by genetics. A functional variant in GPR126 gene region was significantly associated with DLCO/VA. Pulmonary GPR126 expression was decreased in patients with COPD.

scholarly journals Genotypic and Phenotypic Characterization of Lettuce Bacterial Pathogen Xanthomonas hortorum pv. vitians Populations Collected in Quebec, Canada

Agronomy ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2386
Author(s):  
Pierre-Olivier Hébert ◽  
Martin Laforest ◽  
Dong Xu ◽  
Marie Ciotola ◽  
Mélanie Cadieux ◽  
...  
Keyword(s):  
Leaf Spot ◽  
Genome Wide Association Study ◽  
De Novo ◽  
Association Studies ◽  
Genome Wide Association ◽  
Phenotypic Characterization ◽  
Genome Wide Association Studies ◽  
Bacterial Leaf Spot ◽  
Eastern Canada ◽  
Genome Wide

Bacterial leaf spot of lettuce, caused by Xanthomonas hortorum pv. vitians, is an economically important disease worldwide. For instance, it caused around 4 million CAD in losses in only a few months during the winter of 1992 in Florida. Because only one pesticide is registered to control this disease in Canada, the development of lettuce cultivars tolerant to bacterial leaf spot remains the most promising approach to reduce the incidence and severity of the disease in lettuce fields. The lack of information about the genetic diversity of the pathogen, however, impairs breeding programs, especially when disease resistance is tested on newly developed lettuce germplasm lines. To evaluate the diversity of X. hortorum pv. vitians, a multilocus sequence analysis was performed on 694 isolates collected in Eastern Canada through the summers of 2014 to 2017 and two isolates in 1996 and 2007. All isolates tested were clustered into five phylogroups. Six pathotypes were identified following pathogenicity tests conducted in greenhouses, but when phylogroups were compared with pathotypes, no correlation could be drawn. However, in vitro production of xanthan and xanthomonadins was investigated, and isolates with higher production of xanthomonadins were generally causing less severe symptoms on the tolerant cultivar Little Gem. Whole-genome sequencing was undertaken for 95 isolates belonging to the pathotypes identified, and de novo assembly made with reads unmapped to the reference strain’s genome sequence resulted in 694 contigs ranging from 128 to 120,795 bp. Variant calling was performed prior to genome-wide association studies computed with single-nucleotide polymorphisms (SNPs), copy-number variants and gaps. Polymorphisms with significant p-values were only found on the cultivar Little Gem. Our results allowed molecular identification of isolates likely to cause bacterial leaf spot of lettuce, using two SNPs identified through genome-wide association study.

scholarly journals Prioritization of genes associated with the pathogenesis of leukosis in cattle

2019 ◽  
Vol 22 (8) ◽  
pp. 1063-1069 ◽  
Author(s):  
N. S. Yudin ◽  
N. L. Podkolodnyy ◽  
T. A. Agarkova ◽  
E. V. Ignatieva
Keyword(s):  
Protein Interactions ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Mammalian Species ◽  
Genome Wide Association ◽  
Farm Animals ◽  
Genome Wide Association Studies ◽  
Protein Protein Interactions ◽  
Genome Wide ◽  
A Genome

Selection by means of genetic markers is a promising approach to the eradication of infectious diseases in farm animals, especially in the absence of effective methods of treatment and prevention. Bovine leukemia virus (BLV) is spread throughout the world and represents one of the biggest problems for the livestock production and food security in Russia. However, recent genome-wide association studies have shown that sensitivity/resistance to BLV is polygenic. The aim of this study was to create a catalog of cattle genes and genes of other mammalian species involved in the pathogenesis of BLV-induced infection and to perform gene prioritization using bioinformatics methods. Based on manually collected information from a range of open sources, a total of 446 genes were included in the catalog of cattle genes and genes of other mammals involved in the pathogenesis of BLV-induced infection. The following criteria were used to prioritize 446 genes from the catalog: (1) the gene is associated with leukemia according to a genome-wide association study; (2) the gene is associated with leukemia according to a case-control study; (3) the role of the gene in leukemia development has been studied using knockout mice; (4) protein-protein interactions exist between the gene-encoded protein and either viral particles or individual viral proteins; (5) the gene is annotated with Gene Ontology terms that are overrepresented for a given list of genes; (6) the gene participates in biological pathways from the KEGG or REACTOME databases, which are over-represented for a given list of genes; (7) the protein encoded by the gene has a high number of protein-protein interactions with proteins encoded by other genes from the catalog. Based on each criterion, a rank was assigned to each gene. Then the ranks were summarized and an overall rank was determined. Prioritization of 446 candidate genes allowed us to identify 5 genes of interest (TNF,LTB,BOLA-DQA1,BOLA-DRB3,ATF2), which can affect the sensitivity/resistance of cattle to leukemia.

scholarly journals Generalizability of Associations from Prostate Cancer Genome-Wide Association Studies in Multiple Populations

2009 ◽  
Vol 18 (4) ◽  
pp. 1285-1289 ◽  
Author(s):  
Kevin M. Waters ◽  
Loic Le Marchand ◽  
Laurence N. Kolonel ◽  
Kristine R. Monroe ◽  
Daniel O. Stram ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Association Studies ◽  
Cancer Genome ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Multiple Populations ◽  
Genome Wide

scholarly journals Heritability and genome-wide association study of diffusing capacity of the lung

2018 ◽  
Vol 52 (3) ◽  
pp. 1800647 ◽  
Author(s):  
Natalie Terzikhan ◽  
Fangui Sun ◽  
Fien M. Verhamme ◽  
Hieab H.H. Adams ◽  
Daan Loth ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Association Studies ◽  
Genome Wide Association ◽  
Considerable Proportion ◽  
Chronic Obstructive ◽  
Genome Wide Association Studies ◽  
Diffusing Capacity ◽  
Human Lung Tissue ◽  
Alveolar Volume ◽  
Genome Wide

Although several genome-wide association studies (GWAS) have investigated the genetics of pulmonary ventilatory function, little is known about the genetic factors that influence gas exchange. The aim of the study was to investigate the heritability of, and genetic variants associated with the diffusing capacity of the lung.GWAS was performed on diffusing capacity of the lung measured by carbon monoxide uptake (DLCO) and per alveolar volume (VA) using the single-breath technique, in 8372 individuals from two population-based cohort studies, the Rotterdam Study and the Framingham Heart Study. Heritability was estimated in related (n=6246) and unrelated (n=3286) individuals.Heritability of DLCO and DLCO/VA ranged between 23% and 28% in unrelated individuals and between 45% and 49% in related individuals. Meta-analysis identified a genetic variant in ADGRG6 that is significantly associated with DLCO/VA. Gene expression analysis of ADGRG6 in human lung tissue revealed a decreased expression in patients with chronic obstructive pulmonary disease (COPD) and subjects with decreased DLCO/VA.DLCO and DLCO/VA are heritable traits, with a considerable proportion of variance explained by genetics. A functional variant in ADGRG6 gene region was significantly associated with DLCO/VA. Pulmonary ADGRG6 expression was decreased in patients with COPD.

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