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Journal of Infection and Public Health Oct 2023Dengue is caused by the dengue virus (DENVs) infection and clinical manifestations include dengue fever (DF), dengue hemorrhagic fever (DHF), or dengue shock syndrome...
Dengue is caused by the dengue virus (DENVs) infection and clinical manifestations include dengue fever (DF), dengue hemorrhagic fever (DHF), or dengue shock syndrome (DSS). Due to a lack of antiviral drugs and effective vaccines, several therapeutic and control strategies have been proposed. A systemic literature review was conducted according to PRISMA guidelines to select proper references to give an overview of DENV infection. Results indicate that understanding the virus characteristics and epidemiology are essential to gain the basic and clinical knowledge as well as dengue disseminated pattern and status. Different factors and mechanisms are thought to be involved in the presentation of DHF and DSS, including antibody-dependent enhancement, immune dysregulation, viral virulence, host genetic susceptibility, and preexisting dengue antibodies. This study suggests that dissecting pathogenesis and risk factors as well as developing different types of therapeutic and control strategies against DENV infection are urgently needed.
Topics: Humans; Antiviral Agents; Dengue; Genetic Predisposition to Disease; Risk Factors; Virulence
PubMed: 37595484
DOI: 10.1016/j.jiph.2023.08.001 -
Nature Oct 2023High-throughput proteomics platforms measuring thousands of proteins in plasma combined with genomic and phenotypic information have the power to bridge the gap between... (Comparative Study)
Comparative Study
High-throughput proteomics platforms measuring thousands of proteins in plasma combined with genomic and phenotypic information have the power to bridge the gap between the genome and diseases. Here we performed association studies of Olink Explore 3072 data generated by the UK Biobank Pharma Proteomics Project on plasma samples from more than 50,000 UK Biobank participants with phenotypic and genotypic data, stratifying on British or Irish, African and South Asian ancestries. We compared the results with those of a SomaScan v4 study on plasma from 36,000 Icelandic people, for 1,514 of whom Olink data were also available. We found modest correlation between the two platforms. Although cis protein quantitative trait loci were detected for a similar absolute number of assays on the two platforms (2,101 on Olink versus 2,120 on SomaScan), the proportion of assays with such supporting evidence for assay performance was higher on the Olink platform (72% versus 43%). A considerable number of proteins had genomic associations that differed between the platforms. We provide examples where differences between platforms may influence conclusions drawn from the integration of protein levels with the study of diseases. We demonstrate how leveraging the diverse ancestries of participants in the UK Biobank helps to detect novel associations and refine genomic location. Our results show the value of the information provided by the two most commonly used high-throughput proteomics platforms and demonstrate the differences between them that at times provides useful complementarity.
Topics: Humans; Africa; Asia, Southern; Biological Specimen Banks; Blood Proteins; Datasets as Topic; Disease Susceptibility; Genome, Human; Genomics; Genotype; Iceland; Ireland; Phenotype; Plasma; Proteome; Proteomics; Quantitative Trait Loci; United Kingdom
PubMed: 37794188
DOI: 10.1038/s41586-023-06563-x -
European Heart Journal Sep 2023Previous evidence has mainly supported transient changes in cardiac function during interictal or peri-ictal phases in people with epilepsy, but the long-term risk of...
BACKGROUND AND AIMS
Previous evidence has mainly supported transient changes in cardiac function during interictal or peri-ictal phases in people with epilepsy, but the long-term risk of cardiac arrhythmias is poorly described. This study aimed to assess the long-term association of epilepsy with cardiac arrhythmias, considering the potential role of genetic predisposition and antiseizure medications (ASMs) in any associations observed.
METHODS
This population-based study evaluated UK Biobank data for individuals recruited between 2006 and 2010. Cox proportional hazards models and competing risk models were used to examine the association of epilepsy history with the long-term incidence risk of cardiac arrhythmias and arrhythmias subtypes. Polygenic risk scores (PRS) were calculated to investigate the effect of genetic susceptibility. The role of ASMs was also evaluated by integrating observational and drug target Mendelian randomization (MR) evidence.
RESULTS
The study included 329 432 individuals, including 2699 people with epilepsy. Compared with those without epilepsy, people with epilepsy experienced an increased risk of all cardiac arrhythmias [hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.21-1.53], atrial fibrillation (HR 1.26, 95% CI 1.08-1.46), and other cardiac arrhythmias (HR 1.56, 95% CI 1.34-1.81). The associations were not modified by genetic predisposition as indicated by PRS. Competing and sensitivity analyses corroborated these results. Individuals with epilepsy using ASMs, especially carbamazepine and valproic acid, were at a higher risk for cardiac arrhythmias. This observation was further supported by drug target MR results (PSMR < .05 and PHEIDI > .05).
CONCLUSION
This study revealed the higher risk of cardiac arrhythmias persists long term in people with epilepsy, especially among those using carbamazepine and valproic acid. These findings highlight the need for regular heart rhythm monitoring and management in people with epilepsy in order to reduce the risk of further cardiovascular complications.
Topics: Humans; Atrial Fibrillation; Carbamazepine; Epilepsy; Genetic Predisposition to Disease; Valproic Acid
PubMed: 37602368
DOI: 10.1093/eurheartj/ehad523 -
The Lancet. Healthy Longevity Jan 2024Rheumatoid arthritis is a chronic autoimmune disorder that affects life expectancy. Accelerated biological ageing is thought to be a major risk factor for age-related...
Associations between biological ageing and the risk of, genetic susceptibility to, and life expectancy associated with rheumatoid arthritis: a secondary analysis of two observational studies.
BACKGROUND
Rheumatoid arthritis is a chronic autoimmune disorder that affects life expectancy. Accelerated biological ageing is thought to be a major risk factor for age-related diseases, but its role in rheumatoid arthritis remains uncertain. We aimed to assess the associations between biological ageing and risk of rheumatoid arthritis and genetic susceptibility to the disease. We also aimed to assess the effect of biological ageing on the life expectancy of people with rheumatoid arthritis.
METHODS
We calculated the chronological age-adjusted biological age-by both the Klemera-Doubal method (KDMAge) and phenotypic age (PhenoAge)-as a surrogate measure for biological ageing in participants from the US National Health and Nutrition Examination Survey (NHANES) and UK Biobank study. KDMAge or PhenoAge acceleration was defined as the residual of the regression of KDMAge or PhenoAge based on chronological age. Participants with accelerated biological ageing had KDMAge or PhenoAge acceleration values greater than 0, whereas those without accelerated ageing had values less than or equal to 0. We did cross-sectional analyses to assess the association between biological ageing and prevalent rheumatoid arthritis in both cohorts and prospective analyses to assess the association between biological ageing and incident rheumatoid arthritis in the UK Biobank. Logistic regression and Cox proportional hazards models were used to analyse these associations. Polygenic risk scores were used to establish genetic susceptibility to rheumatoid arthritis and to analyse the interaction between biological ageing and genetic risk. We also assessed the association between life expectancy and biological ageing status in people with rheumatoid arthritis.
FINDINGS
In the cross-sectional analyses, each 1-year increase in age-adjusted biological age was associated with an increase in the risk of rheumatoid arthritis of between 1% and 10%. In the NHANES, individuals with accelerated ageing had a higher risk of rheumatoid arthritis than non-accelerated ageing individuals, with odds ratios of 1·21 (95% CI 1·03-1·42; p=0·018) for KDMAge acceleration and 1·46 (1·26-1·69; p<0·0001) for PhenoAge acceleration. Similarly, in the UK Biobank, the risk of rheumatoid arthritis was increased in individuals with accelerated ageing compared with individuals with no accelerated ageing (KDMAge odds ratio 1·96 [95% CI 1·71-2·24]; PhenoAge 2·71 [2·51-2·92]). In the prospective analyses of the UK Biobank population, accelerated biological ageing was associated with an increased risk of incident rheumatoid arthritis as measured by both KDMAge (hazard ratio 1·27 [95% CI 1·03-1·55]) and PhenoAge (1·70 [1·52-1·92]). Among participants with high genetic predisposition to rheumatoid arthritis, accelerated biological ageing was associated with an increased risk of incident disease, and we noted significant additive interactions between accelerated biological ageing and genetic risk. At age 45 years, people with rheumatoid arthritis had reduced life expectancy compared with those without rheumatoid arthritis. Among people with rheumatoid arthritis, accelerated biological ageing was associated with reduced life expectancy compared with not having accelerated biological ageing.
INTERPRETATION
Accelerated biological ageing could increase the risk of rheumatoid arthritis, especially among people with high genetic risk, and could reduce the life expectancy of people with rheumatoid arthritis. The identification of populations with accelerated biological ageing has important implications for reducing the risk of rheumatoid arthritis and of lowered life expectancy.
FUNDING
National Natural Science Foundation of China.
Topics: Humans; Nutrition Surveys; Prospective Studies; Cross-Sectional Studies; Aging; Genetic Predisposition to Disease; Life Expectancy; Arthritis, Rheumatoid
PubMed: 38081205
DOI: 10.1016/S2666-7568(23)00220-9 -
Science China. Life Sciences Jul 2023With the exception of an extremely small number of cases caused by single gene mutations, most autoimmune diseases result from the complex interplay between... (Review)
Review
With the exception of an extremely small number of cases caused by single gene mutations, most autoimmune diseases result from the complex interplay between environmental and genetic factors. In a nutshell, etiology of the common autoimmune disorders is unknown in spite of progress elucidating certain effector cells and molecules responsible for pathologies associated with inflammatory and tissue damage. In recent years, population genetics approaches have greatly enriched our knowledge regarding genetic susceptibility of autoimmunity, providing us with a window of opportunities to comprehensively re-examine autoimmunity-associated genes and possible pathways. In this review, we aim to discuss etiology and pathogenesis of common autoimmune disorders from the perspective of human genetics. An overview of the genetic basis of autoimmunity is followed by 3 chapters detailing susceptibility genes involved in innate immunity, adaptive immunity and inflammatory cell death processes respectively. With such attempts, we hope to expand the scope of thinking and bring attention to lesser appreciated molecules and pathways as important contributors of autoimmunity beyond the 'usual suspects' of a limited subset of validated therapeutic targets.
Topics: Humans; Autoimmune Diseases; Immunity, Innate; Autoimmunity; Adaptive Immunity; Genetic Predisposition to Disease
PubMed: 36738430
DOI: 10.1007/s11427-021-2187-3 -
Nature May 2024The gut microbiota operates at the interface of host-environment interactions to influence human homoeostasis and metabolic networks. Environmental factors that...
The gut microbiota operates at the interface of host-environment interactions to influence human homoeostasis and metabolic networks. Environmental factors that unbalance gut microbial ecosystems can therefore shape physiological and disease-associated responses across somatic tissues. However, the systemic impact of the gut microbiome on the germline-and consequently on the F offspring it gives rise to-is unexplored. Here we show that the gut microbiota act as a key interface between paternal preconception environment and intergenerational health in mice. Perturbations to the gut microbiota of prospective fathers increase the probability of their offspring presenting with low birth weight, severe growth restriction and premature mortality. Transmission of disease risk occurs via the germline and is provoked by pervasive gut microbiome perturbations, including non-absorbable antibiotics or osmotic laxatives, but is rescued by restoring the paternal microbiota before conception. This effect is linked with a dynamic response to induced dysbiosis in the male reproductive system, including impaired leptin signalling, altered testicular metabolite profiles and remapped small RNA payloads in sperm. As a result, dysbiotic fathers trigger an elevated risk of in utero placental insufficiency, revealing a placental origin of mammalian intergenerational effects. Our study defines a regulatory 'gut-germline axis' in males, which is sensitive to environmental exposures and programmes offspring fitness through impacting placenta function.
Topics: Animals; Female; Male; Mice; Pregnancy; Dysbiosis; Fathers; Gastrointestinal Microbiome; Leptin; Mice, Inbred C57BL; Placenta; Placental Insufficiency; Pregnancy Outcome; Prenatal Injuries; Signal Transduction; Spermatozoa; Testis; Disease Susceptibility
PubMed: 38693261
DOI: 10.1038/s41586-024-07336-w -
Nature Medicine Oct 2023Fatty liver disease (FLD) caused by metabolic dysfunction is the leading cause of liver disease and the prevalence is rising, especially in women. Although during...
Fatty liver disease (FLD) caused by metabolic dysfunction is the leading cause of liver disease and the prevalence is rising, especially in women. Although during reproductive age women are protected against FLD, for still unknown and understudied reasons some develop rapidly progressive disease at the menopause. The patatin-like phospholipase domain-containing 3 (PNPLA3) p.I148M variant accounts for the largest fraction of inherited FLD variability. In the present study, we show that there is a specific multiplicative interaction between female sex and PNPLA3 p.I148M in determining FLD in at-risk individuals (steatosis and fibrosis, P < 10; advanced fibrosis/hepatocellular carcinoma, P = 0.034) and in the general population (P < 10 for alanine transaminase levels). In individuals with obesity, hepatic PNPLA3 expression was higher in women than in men (P = 0.007) and in mice correlated with estrogen levels. In human hepatocytes and liver organoids, PNPLA3 was induced by estrogen receptor-α (ER-α) agonists. By chromatin immunoprecipitation and luciferase assays, we identified and characterized an ER-α-binding site within a PNPLA3 enhancer and demonstrated via CRISPR-Cas9 genome editing that this sequence drives PNPLA3 p.I148M upregulation, leading to lipid droplet accumulation and fibrogenesis in three-dimensional multilineage spheroids with stellate cells. These data suggest that a functional interaction between ER-α and PNPLA3 p.I148M variant contributes to FLD in women.
Topics: Animals; Female; Humans; Male; Mice; Acyltransferases; Carcinoma, Hepatocellular; Fibrosis; Genetic Predisposition to Disease; Liver; Liver Neoplasms; Non-alcoholic Fatty Liver Disease; Phospholipases A2, Calcium-Independent; Receptors, Estrogen
PubMed: 37749332
DOI: 10.1038/s41591-023-02553-8 -
BMC Medicine Sep 2023Diets rich in plant-based foods are associated with lower risks of non-alcoholic fatty liver disease (NAFLD), while the prospective evidence is limited. We aimed to...
BACKGROUND
Diets rich in plant-based foods are associated with lower risks of non-alcoholic fatty liver disease (NAFLD), while the prospective evidence is limited. We aimed to examine longitudinal associations of plant-based diets and genetic susceptibility with NAFLD risk.
METHODS
This longitudinal cohort study included 159,222 participants (58.0 ± 8.0 years old, 55.7% female) free of NAFLD in the UK Biobank. We calculated the overall plant-based diet index (PDI), the healthful plant-based diet index (hPDI), and the unhealthful plant-based diet index (uPDI). New-onset NAFLD was the primary outcome. The weighted polygenic risk score was calculated based on risk variants associated with NAFLD. Hazard ratios (HR) and 95% confidential intervals (CI) were estimated by Cox proportional hazards model. Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) measured liver fat content in a subsample of 20,692 participants (57.5 ± 7.4 years old, 52.6% female) was the secondary outcome. The associations between plant-based diet indices and MRI-PDFF were evaluated using generalized linear models.
RESULTS
During a median follow-up of 9.5 years, 1541 new-onset NAFLD cases were documented. Compared to the lowest quintile, multivariable-adjusted hazard ratios (HRs) of NAFLD in the highest quintile were 0.78 (95% confidential intervals [CI], 0.66-0.93, p-trend =0.02), 0.74 (95% CI, 0.62-0.87, p-trend <0.0001), and 1.24 (95% CI, 1.05-1.46, p-trend = 0.02) for overall PDI, hPDI, and uPDI, respectively. For liver fat content, higher overall PDI and hPDI were associated with lower MRI-PDFF, while higher uPDI was associated with higher liver fat content. We observed a significant interaction between hPDI and PRS (p-interaction =0.03), and the NAFLD risk was lowest among participants with the highest hPDI and low genetic risk.
CONCLUSIONS
Higher intake of plant-based diets especially healthful plant-based diets was associated with lower NAFLD risk and liver fat content regardless of genetic susceptibility, whereas an unhealthful plant-based diet was associated with higher NAFLD risk and intrahepatic steatosis. These results suggest that the quality of plant-based foods should be highlighted when adopting a plant-based diet.
Topics: Humans; Middle Aged; Aged; Non-alcoholic Fatty Liver Disease; Genetic Predisposition to Disease; Longitudinal Studies; Prospective Studies; Diet; Diet, Vegetarian
PubMed: 37697334
DOI: 10.1186/s12916-023-03028-w -
Current Opinion in Psychology Feb 2024Misinformation poses a significant concern, promoting false beliefs and eroding trust in media. People differ in their susceptibility to believe and to share... (Review)
Review
Misinformation poses a significant concern, promoting false beliefs and eroding trust in media. People differ in their susceptibility to believe and to share misinformation. In this article, we reviewed recent research on relationships between personality traits and belief in and sharing of misinformation. Findings show that more extroverted and less conscientious and agreeable people tend to be more susceptible to believing in and sharing misinformation. Additionally, the Dark Triad personality traits of narcissism, psychopathy, and Machiavellianism tend to be positively associated with sharing of misinformation, and narcissism and psychopathy are associated with greater belief in misinformation. Understanding these individual differences can inform interventions to reduce the effects of misinformation.
Topics: Humans; Personality; Machiavellianism; Antisocial Personality Disorder; Narcissism; Disease Susceptibility
PubMed: 38065004
DOI: 10.1016/j.copsyc.2023.101752 -
Molecular Cancer May 2024Aging and cancer exhibit apparent links that we will examine in this review. The null hypothesis that aging and cancer coincide because both are driven by time,... (Review)
Review
Aging and cancer exhibit apparent links that we will examine in this review. The null hypothesis that aging and cancer coincide because both are driven by time, irrespective of the precise causes, can be confronted with the idea that aging and cancer share common mechanistic grounds that are referred to as 'hallmarks'. Indeed, several hallmarks of aging also contribute to carcinogenesis and tumor progression, but some of the molecular and cellular characteristics of aging may also reduce the probability of developing lethal cancer, perhaps explaining why very old age (> 90 years) is accompanied by a reduced incidence of neoplastic diseases. We will also discuss the possibility that the aging process itself causes cancer, meaning that the time-dependent degradation of cellular and supracellular functions that accompanies aging produces cancer as a byproduct or 'age-associated disease'. Conversely, cancer and its treatment may erode health and drive the aging process, as this has dramatically been documented for cancer survivors diagnosed during childhood, adolescence, and young adulthood. We conclude that aging and cancer are connected by common superior causes including endogenous and lifestyle factors, as well as by a bidirectional crosstalk, that together render old age not only a risk factor of cancer but also an important parameter that must be considered for therapeutic decisions.
Topics: Humans; Aging; Neoplasms; Animals; Disease Susceptibility; Risk Factors
PubMed: 38760832
DOI: 10.1186/s12943-024-02020-z