scholarly journals The landscape of genetic susceptibility correlations among diseases and traits

2017 ◽  
Vol 24 (5) ◽  
pp. 921-926 ◽  
Author(s):  
Jung Hun Ohn

Abstract Objective: The aim of the study was to comprehensively explore the genetic susceptibility correlations among diseases and traits from large-scale individual genotype data. Materials and Methods: Based on a knowledge base of genetic variants significantly (P < 5 × 10−8) linked with human phenotypes, genetic risk scores (GRSs) of diseases or traits were calculated for 2504 individuals with whole-genome sequencing data from the 1000 Genomes Project. Associations between diseases/traits were statistically evaluated by pairwise correlation analysis of GRSs. Overlaps between the genetic susceptibility correlations and disease comorbidity associations from hospital claims data in more than 30 million patients in United States were assessed. Results: Correlation analysis of GRSs revealed 823 significant correlations among 78 diseases and 89 traits (false discovery rate adjusted P-value or Q-value < 0.01). It is noticeable that GRSs were correlated in 464 associations (56.4%) even if they were combinations of distinct sets of risk variants without chromosomal linkage, suggesting the presence of genetic interactions beyond chromosome position. When 312 significant genetic susceptibility correlations between diseases were compared to nationwide disease comorbidity correlations obtained from data from 32 million Medicare claims in the United States, 108 overlaps (34.6%) were found that had both genetic susceptibility and epidemiologic comorbid correlations. Conclusion: The study suggests that common genetic background exists between diseases and traits with epidemiologic associations. The GRS correlation approach provides a rich source of candidate associations among diseases and traits from the genetic perspective, warranting further epidemiologic studies.

2018 ◽  
Vol 69 (3) ◽  
pp. 428-437 ◽  
Author(s):  
Eelco Franz ◽  
Ovidiu Rotariu ◽  
Bruno S Lopes ◽  
Marion MacRae ◽  
James L Bono ◽  
...  

AbstractBackgroundShiga toxin–producing Escherchia coli (STEC) O157:H7 is a zoonotic pathogen that causes numerous food and waterborne disease outbreaks. It is globally distributed, but its origin and the temporal sequence of its geographical spread are unknown.MethodsWe analyzed whole-genome sequencing data of 757 isolates from 4 continents, and performed a pan-genome analysis to identify the core genome and, from this, extracted single-nucleotide polymorphisms. A timed phylogeographic analysis was performed on a subset of the isolates to investigate its worldwide spread.ResultsThe common ancestor of this set of isolates occurred around 1890 (1845–1925) and originated from the Netherlands. Phylogeographic analysis identified 34 major transmission events. The earliest were predominantly intercontinental, moving from Europe to Australia around 1937 (1909–1958), to the United States in 1941 (1921–1962), to Canada in 1960 (1943–1979), and from Australia to New Zealand in 1966 (1943–1982). This pre-dates the first reported human case of E. coli O157:H7, which was in 1975 from the United States.ConclusionsInter- and intra-continental transmission events have resulted in the current international distribution of E. coli O157:H7, and it is likely that these events were facilitated by animal movements (eg, Holstein Friesian cattle). These findings will inform policy on action that is crucial to reduce the further spread of E. coli O157:H7 and other (emerging) STEC strains globally.


2019 ◽  
Vol 85 (23) ◽  
Author(s):  
Shaokang Zhang ◽  
Hendrik C. den Bakker ◽  
Shaoting Li ◽  
Jessica Chen ◽  
Blake A. Dinsmore ◽  
...  

ABSTRACT SeqSero, launched in 2015, is a software tool for Salmonella serotype determination from whole-genome sequencing (WGS) data. Despite its routine use in public health and food safety laboratories in the United States and other countries, the original SeqSero pipeline is relatively slow (minutes per genome using sequencing reads), is not optimized for draft genome assemblies, and may assign multiple serotypes for a strain. Here, we present SeqSero2 (github.com/denglab/SeqSero2; denglab.info/SeqSero2), an algorithmic transformation and functional update of the original SeqSero. Major improvements include (i) additional sequence markers for identification of Salmonella species and subspecies and certain serotypes, (ii) a k-mer based algorithm for rapid serotype prediction from raw reads (seconds per genome) and improved serotype prediction from assemblies, and (iii) a targeted assembly approach for specific retrieval of serotype determinants from WGS for serotype prediction, new allele discovery, and prediction troubleshooting. Evaluated using 5,794 genomes representing 364 common U.S. serotypes, including 2,280 human isolates of 117 serotypes from the National Antimicrobial Resistance Monitoring System, SeqSero2 is up to 50 times faster than the original SeqSero while maintaining equivalent accuracy for raw reads and substantially improving accuracy for assemblies. SeqSero2 further suggested that 3% of the tested genomes contained reads from multiple serotypes, indicating a use for contamination detection. In addition to short reads, SeqSero2 demonstrated potential for accurate and rapid serotype prediction directly from long nanopore reads despite base call errors. Testing of 40 nanopore-sequenced genomes of 17 serotypes yielded a single H antigen misidentification. IMPORTANCE Serotyping is the basis of public health surveillance of Salmonella. It remains a first-line subtyping method even as surveillance continues to be transformed by whole-genome sequencing. SeqSero allows the integration of Salmonella serotyping into a whole-genome-sequencing-based laboratory workflow while maintaining continuity with the classic serotyping scheme. SeqSero2, informed by extensive testing and application of SeqSero in the United States and other countries, incorporates important improvements and updates that further strengthen its application in routine and large-scale surveillance of Salmonella by whole-genome sequencing.


Author(s):  
Epiphanie Nyirabahizi ◽  
Gregory H. Tyson ◽  
Heather Tate ◽  
Michael S. Williams ◽  
Gurinder S. Saini ◽  
...  

As part of the National Antimicrobial Resistance Monitoring System (NARMS) activities, the United States Department of Agriculture (USDA) Food Safety Inspection Service (FSIS) collected cecal samples from food animal slaughter facilities throughout the country between 2014 and 2018. Of the 26,780 cecal samples from cattle, swine, chicken and turkey , 6,350 (23.71%) tested positive for Salmonella . NARMS tested Salmonella for susceptibility to aminoglycosides, folate pathway inhibitors, macrolides, phenicols, quinolones, beta lactams, and tetracyclines. Using the regional subdivisions defined in the USDA Office of Investigation, we used chi-square test to assess potential association between the region from which the samples were collected and both Salmonella prevalence and susceptibility. The results show a significant association between region and Salmonella prevalence, when accounting for source and establishment size, with the southeast region having the highest probability of finding Salmonella . However, the western region had the highest resistance probability across all antimicrobial classes except for macrolides, which showed no regional association. This association between region and resistance was strongest among isolates from cattle. Analysis of whole-genome sequencing data indicated that a significantly higher prevalence of Salmonella Newport in cattle in the western region (accounting for 9.52% of cattle isolates, compared to 3.44% in other regions) may account for the greater resistance to multiple drug classes. Approximately 90% of Salmonella Newport in the west exhibited the MDR-AmpC phenotype encoded by aph(3'')-Ib/aph(6)-Id , bla CMY-2 , floR , sul2 , and tetA. . Thus, differences in resistance across regions may be due to geographical differences in the prevalence of specific Salmonella serotypes and their accompanying resistance genes.


1966 ◽  
Vol 05 (02) ◽  
pp. 67-74 ◽  
Author(s):  
W. I. Lourie ◽  
W. Haenszeland

Quality control of data collected in the United States by the Cancer End Results Program utilizing punchcards prepared by participating registries in accordance with a Uniform Punchcard Code is discussed. Existing arrangements decentralize responsibility for editing and related data processing to the local registries with centralization of tabulating and statistical services in the End Results Section, National Cancer Institute. The most recent deck of punchcards represented over 600,000 cancer patients; approximately 50,000 newly diagnosed cases are added annually.Mechanical editing and inspection of punchcards and field audits are the principal tools for quality control. Mechanical editing of the punchcards includes testing for blank entries and detection of in-admissable or inconsistent codes. Highly improbable codes are subjected to special scrutiny. Field audits include the drawing of a 1-10 percent random sample of punchcards submitted by a registry; the charts are .then reabstracted and recoded by a NCI staff member and differences between the punchcard and the results of independent review are noted.


Author(s):  
Joshua Kotin

This book is a new account of utopian writing. It examines how eight writers—Henry David Thoreau, W. E. B. Du Bois, Osip and Nadezhda Mandel'shtam, Anna Akhmatova, Wallace Stevens, Ezra Pound, and J. H. Prynne—construct utopias of one within and against modernity's two large-scale attempts to harmonize individual and collective interests: liberalism and communism. The book begins in the United States between the buildup to the Civil War and the end of Jim Crow; continues in the Soviet Union between Stalinism and the late Soviet period; and concludes in England and the United States between World War I and the end of the Cold War. In this way it captures how writers from disparate geopolitical contexts resist state and normative power to construct perfect worlds—for themselves alone. The book contributes to debates about literature and politics, presenting innovative arguments about aesthetic difficulty, personal autonomy, and complicity and dissent. It models a new approach to transnational and comparative scholarship, combining original research in English and Russian to illuminate more than a century and a half of literary and political history.


Author(s):  
Anne Nassauer

This book provides an account of how and why routine interactions break down and how such situational breakdowns lead to protest violence and other types of surprising social outcomes. It takes a close-up look at the dynamic processes of how situations unfold and compares their role to that of motivations, strategies, and other contextual factors. The book discusses factors that can draw us into violent situations and describes how and why we make uncommon individual and collective decisions. Covering different types of surprise outcomes from protest marches and uprisings turning violent to robbers failing to rob a store at gunpoint, it shows how unfolding situations can override our motivations and strategies and how emotions and culture, as well as rational thinking, still play a part in these events. The first chapters study protest violence in Germany and the United States from 1960 until 2010, taking a detailed look at what happens between the start of a protest and the eruption of violence or its peaceful conclusion. They compare the impact of such dynamics to the role of police strategies and culture, protesters’ claims and violent motivations, the black bloc and agents provocateurs. The analysis shows how violence is triggered, what determines its intensity, and which measures can avoid its outbreak. The book explores whether we find similar situational patterns leading to surprising outcomes in other types of small- and large-scale events: uprisings turning violent, such as Ferguson in 2014 and Baltimore in 2015, and failed armed store robberies.


Author(s):  
Richard Gowan

During Ban Ki-moon’s tenure, the Security Council was shaken by P5 divisions over Kosovo, Georgia, Libya, Syria, and Ukraine. Yet it also continued to mandate and sustain large-scale peacekeeping operations in Africa, placing major burdens on the UN Secretariat. The chapter will argue that Ban initially took a cautious approach to controversies with the Council, and earned a reputation for excessive passivity in the face of crisis and deference to the United States. The second half of the chapter suggests that Ban shifted to a more activist pressure as his tenure went on, pressing the Council to act in cases including Côte d’Ivoire, Libya, and Syria. The chapter will argue that Ban had only a marginal impact on Council decision-making, even though he made a creditable effort to speak truth to power over cases such as the Central African Republic (CAR), challenging Council members to live up to their responsibilities.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S563-S563
Author(s):  
Kenneth A Valles ◽  
Lewis R Roberts

Abstract Background Infection by hepatitis B and C viruses causes inflammation of the liver and can lead to cirrhosis, liver failure, and hepatocellular carcinoma. The WHO’s ambition to eliminate viral hepatitis by 2030 requires strategies specific to the dynamic disease profiles each nation faces. Large-scale human movement from high-prevalence nations to the United States and Canada have altered the disease landscape, likely warranting adjustments to present elimination approaches. However, the nature and magnitude of the new disease burden remains unknown. This study aims to generate a modeled estimate of recent HBV and HCV prevalence changes to the United States and Canada due to migration. Methods Total migrant populations from 2010-2019 were obtained from United Nations Migrant Stock database. Country-of-origin HBV and HCV prevalences were obtained for the select 40 country-of-origin nations from the Polaris Observatory and systematic reviews. A standard pivot table was used to evaluate the disease contribution from and to each nation. Disease progression estimates were generated using the American Association for the Study of the Liver guidelines and outcome data. Results Between 2010 and 2019, 7,676,937 documented migrants arrived in US and Canada from the selected high-volume nations. Primary migrant source regions were East Asia and Latin America. Combined, an estimated 878,995 migrants were HBV positive, and 226,428 HCV positive. The majority of both migrants (6,477,506) and new viral hepatitis cases (HBV=840,315 and HCV=215,359) were found in the United States. The largest source of HBV cases stemmed from the Philippines, and HCV cases from El Salvador. Conclusion Massive human movement has significantly changed HBV and HCV disease burdens in both the US and Canada over the past decade and the long-term outcomes of cirrhosis and HCC are also expected to increase. These increases are likely to disproportionally impact individuals of the migrant and refugee communities and screening and treatment programs must be strategically adjusted in order to reduce morbidity, mortality, and healthcare expenses. Disclosures All Authors: No reported disclosures


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