Genetic factors may play a prominent role in the development of coronary heart disease dependent on important environmental factors.
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ABSTRACT:
SUBMITTER: Song C
PROVIDER: S-EPMC4288985 | biostudies-literature | 2014 Jun
REPOSITORIES: biostudies-literature
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Project description:Over the past 2 decades, DNA samples from thousands of families have been collected and genotyped for linkage studies of common complex diseases, such as type 2 diabetes, asthma, and prostate cancer. Unfortunately, little success has been achieved in identifying genetic susceptibility risk factors through these considerable efforts. However, significant success in identifying common disease risk-associated variants has been recently achieved from genome-wide association studies using unrelated case-control samples. These genome-wide association studies are typically done using population-based cases and controls that are ascertained irrespective of their family history for the disease of interest. Few genetic association studies have taken full advantage of the considerable resources that are available from the linkage-based family collections despite evidence showing cases that have a positive family history of disease are more likely to carry common genetic variants associated with disease susceptibility. Herein, we argue that population stratification is still a concern in case-control genetic association studies, despite the development of analytic methods designed to account for this source of confounding, for a subset of single nucleotide polymorphisms in the genome, most notably those single nucleotide polymorphisms in regions involved with natural selection. We note that current analytic approaches designed to address the issue of population stratification in case-control studies cannot definitively distinguish between true and false associations, and we argue that family-based samples can still serve an invaluable role in following up findings from case-control studies.
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Project description:ObjectiveTo examine the relative contributions of disease activity and psychological factors to self-reported symptoms and disability in children with Crohn's disease.Study designParticipants (n = 127 children age 8-18 years) completed questionnaires on symptom severity and disability, as well as psychological measures assessing anxiety, depression, pain beliefs and coping. Disease activity was measured by the Pediatric Crohn's Disease Activity Index. Structural equation modeling was used to test the effects of disease activity and psychological factors on symptoms and disability.ResultsIn the hypothesized model predicting symptoms, psychological factors (β = 0.58; P < .001) were significantly associated with disease symptoms but disease activity was not. The model for disability yielded significant associations for both psychological factors (β = 0.75; P < .001) and disease activity (β = 0.61, P < .05).ConclusionCrohn's disease symptoms in children and adolescents are not only driven by disease activity. Coping, anxiety, depression, and cognition of illness are important in the patient-reporting of symptom severity and disability. Physicians need to be aware that symptom self-reporting can be driven by psychological factors and may not always be simply an indicator of disease activity.Trial registrationClinicalTrials.gov: NCT00679003.
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Project description:BACKGROUND:Coronary heart disease (CHD) is a complex disease caused by multi-factors and a major threat to human health. Circular RNAs (circRNAs) have critical roles in various biological processes and diseases. This study explores the independent role of circRNAs and their interaction with environmental factors in CHD. METHODS:A case-control study was conducted from March 2015 to September 2017 in Fuzhou, China. A total of 585 CHD patients and 585 gender- and age-matched healthy controls were enrolled. Questionnaire survey, health examination and molecular biology laboratory testing were conducted. Microarray technology and quantitative real-time polymerase chain reaction (PCR) were used to profile the expression levels of circRNAs. The area under the curve (AUC) of the receiver operating characteristic (ROC) was used to determine the diagnostic cut-offs. Multivariate logistic regression and multiplicative analysis were used to analyse the effects of environmental factors and hsa_circ_0008507, hsa_circ_0001946, hsa_circ_0000284 and hsa_circ_0125589 on CHD. RESULTS:The expression profile of circRNAs showed that 3423 circRNAs were differentially expressed at P < 0.05, but none pass multiple testing correction. qRT-PCR further confirmed the expression levels of hsa_circ_0008507, hsa_circ_0001946 and hsa_circ_0000284 in peripheral blood leukocytes in CHD cases were higher than those in non-CHD subjects (All p < 0.05). Hsa_circ_0008507 (OR = 1.29; 95% CI: 1.11-1.50), hsa_circ_0001946 (OR = 1.20; 95% CI: 1.01-1.42) and hsa_circ_0000284 (OR = 2.05; 95% CI: 1.32-3.19) were independent risk factors for CHD after controlling other common environmental risk factors. The AUC for hsa_circ_0008507, hsa_circ_0001946 and hsa_circ_0000284 was 0.75, 0.71 and 0.68, respectively. Compared with non-smoking individuals with low hsa_circ_0008507 expression, the smokers with high hsa_circ_0008507 expression showed the highest magnitude of OR in CHD risk. Additionally, a statistically significant multiplicative interaction was found between hsa_circ_0008507 and smoking for CHD. CONCLUSIONS:Hsa_circ_0008507, hsa_circ_0001946 and hsa_circ_0000284 were closely related to the occurrence and development of CHD. The combination of smoking and high hsa_circ_0008507 expression causes the occurrence and development of CHD.
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Project description:ObjectiveOver 12% of women in the United States have reduced fertility and/or fecundity. Environmental factors, such as temperature, and socioeconomic factors have been implicated in reducing female fecundity. The purpose of this study is to investigate the effect of environmental factors coupled with socioeconomic factors on birth rate at the country-level. We use birth rate as a proxy for female fecundity. This will enable us to identify the most important factors affecting female fecundity.MethodsUsing country-specific data from 182 countries, we constructed a regression model of the effects of environmental and socioeconomic factors on birth rate at the country-level. Our model assesses the role of temperature, Gross Domestic Product (GDP) per capita, fine air particulate matter (PM 2.5), and prevalence of male and female Body Mass Index (BMI) > = 25 (age-standardized) on birth rate per country. Because many of these factors are inter-dependent, we include all possible two-way interaction terms to assess the role of individual factors and interactions between multiple factors in the model.ResultsIn the full regression model, we found that GDP per capita along with 5 interaction terms were significant after adjusting for multiple testing. Female BMI was only nominally significant. GDP per capita was independently associated with birth rate (adjusted p-value <0.001). Prevalence of BMI > = 25 age-standardized in males and females were also significant when interacting with air pollution or GDP on female fecundity (birth rate). Temperature did not affect birth rate either independently or as an interaction unless BMI was removed from the model.ConclusionA country's economic wealth was the most significant factor in predicting birth rate in a statistical model that includes environmental and socioeconomic variables. This is important for future studies investigating environmental factors involved in increasing or decreasing female fecundity.
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Project description:Unisexual lineages are commonly considered to be short-lived in the evolutionary process as accumulation of deleterious mutations stated by Muller's ratchet. However, the gynogenetic hexaploid gibel carp (Carassius gibelio) with existence over 0.5 million years has wider ecological distribution and higher genetic diversity than its sexual progenitors, which provides an ideal model to investigate the underlying mechanisms on countering Muller's ratchet in unisexual taxa. Unlike other unisexual lineages, the wild populations of gibel carp contain rare and variable proportions of males (1-26%), which are determined via two strategies including genotypic sex determination and temperature-dependent sex determination. Here, we used a maternal gibel carp from strain F to be mated with a genotypic male from strain A+, a temperature-dependent male from strain A+, and a male from another species common carp (Cyprinus carpio), respectively. When the maternal individual was mated with the genotypic male, a variant of gynogenesis was initiated, along with male occurrence, accumulation of microchromosomes, and creation of genetic diversity in the offspring. When the maternal individual was mated with the temperature-dependent male and common carp, typical gynogenesis was initiated that all the offspring showed the same genetic information as the maternal individual. Subsequently, we found out that the genotypic male nucleus swelled and contacted with the female nucleus after fertilization although it was extruded from the female nucleus eventually, which might be associated with the genetic variation in the offspring. These results reveal that genotypic males play an important role in the creation of genetic diversity in gynogenetic gibel carp, which provides insights into the evolution of unisexual reproduction.
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Project description:Direct infusion high-resolution mass spectrometry (DIHRMS) is a novel, high-throughput approach to rapidly and accurately profile hundreds of lipids in human serum without prior chromatography, facilitating in-depth lipid phenotyping for large epidemiological studies to reveal the detailed associations of individual lipids with coronary heart disease (CHD) risk factors. Intact lipid profiling by DIHRMS was performed on 5662 serum samples from healthy participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS). We developed a novel semi-targeted peak-picking algorithm to detect mass-to-charge ratios in positive and negative ionization modes. We analyzed lipid partial correlations, assessed the association of lipid principal components with established CHD risk factors and genetic variants, and examined differences between lipids for a common genetic polymorphism. The DIHRMS method provided information on 360 lipids (including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, and sterol lipids), with a median coefficient of variation of 11.6% (range: 5.4-51.9). The lipids were highly correlated and exhibited a range of associations with clinical chemistry biomarkers and lifestyle factors. This platform can provide many novel insights into the effects of physiology and lifestyle on lipid metabolism, genetic determinants of lipids, and the relationship between individual lipids and CHD risk factors.
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2019-12-18 | PXD007785 | Pride
Project description:The viruses that infect bacteria, known as phages, play a critical role in controlling bacterial populations in many diverse environments, including the human body. This control stems not only from phages killing bacteria but also from the formation of lysogens. In this state, the phage replication cycle is suppressed, and the phage genome is maintained in the bacterial cell in a form known as a prophage. Prophages often carry genes that benefit the host bacterial cell, since increasing the survival of the host cell by extension also increases the fitness of the prophage. These highly diverse and beneficial phage genes, which are not required for the life cycle of the phage itself, have been referred to as "morons," as their presence adds "more on" the phage genome in which they are found. While individual phage morons have been shown to contribute to bacterial virulence by a number of different mechanisms, there have been no systematic investigations of their activities. Using a library of phages that infect two different clinical isolates of P. aeruginosa, PAO1 and PA14, we compared the phenotypes imparted by the expression of individual phage morons. We identified morons that inhibit twitching and swimming motilities and observed an inhibition of the production of virulence factors such as rhamnolipids and elastase. This study demonstrates the scope of phage-mediated phenotypic changes and provides a framework for future studies of phage morons.IMPORTANCE Environmental and clinical isolates of the bacterium Pseudomonas aeruginosa frequently contain viruses known as prophages. These prophages can alter the virulence of their bacterial hosts through the expression of nonessential genes known as "morons." In this study, we identified morons in a group of Pseudomonas aeruginosa phages and characterized the effects of their expression on bacterial behaviors. We found that many morons confer selective advantages for the bacterial host, some of which correlate with increased bacterial virulence. This work highlights the symbiotic relationship between bacteria and prophages and illustrates how phage morons can help bacteria adapt to different selective pressures and contribute to human diseases.
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