共查询到20条相似文献,搜索用时 15 毫秒
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Emily E. Hartwell Alison K. Merikangas Shefali S. Verma Marylyn D. Ritchie Henry R. Kranzler Rachel L. Kember 《Addiction biology》2022,27(1):e13099
Polygenic risk scores (PRS) represent an individual's summed genetic risk for a trait and can serve as biomarkers for disease. Less is known about the utility of PRS as a means to quantify genetic risk for substance use disorders (SUDs) than for many other traits. Nonetheless, the growth of large, electronic health record-based biobanks makes it possible to evaluate the association of SUD PRS with other traits. We calculated PRS for smoking initiation, alcohol use disorder (AUD), and opioid use disorder (OUD) using summary statistics from the Million Veteran Program sample. We then tested the association of each PRS with its primary phenotype in the Penn Medicine BioBank (PMBB) using all available genotyped participants of African or European ancestry (AFR and EUR, respectively) (N = 18,612). Finally, we conducted phenome-wide association analyses (PheWAS) separately by ancestry and sex to test for associations across disease categories. Tobacco use disorder was the most common SUD in the PMBB, followed by AUD and OUD, consistent with the population prevalence of these disorders. All PRS were associated with their primary phenotype in both ancestry groups. PheWAS results yielded cross-trait associations across multiple domains, including psychiatric disorders and medical conditions. SUD PRS were associated with their primary phenotypes; however, they are not yet predictive enough to be useful diagnostically. The cross-trait associations of the SUD PRS are indicative of a broader genetic liability. Future work should extend findings to additional population groups and for other substances of abuse. 相似文献
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Wesley T. Kerr Edward P. Lau Gwen E. Owens Aaron Trefler 《The Yale journal of biology and medicine》2012,85(3):363-377
The electronic health record mandate within the American Recovery andReinvestment Act of 2009 will have a far-reaching affect on medicine. In thisarticle, we provide an in-depth analysis of how this mandate is expected tostimulate the production of large-scale, digitized databases of patientinformation. There is evidence to suggest that millions of patients and theNational Institutes of Health will fully support the mining of such databases tobetter understand the process of diagnosing patients. This data mining likelywill reaffirm and quantify known risk factors for many diagnoses. Thisquantification may be leveraged to further develop computer-aided diagnostictools that weigh risk factors and provide decision support for health careproviders. We expect that creation of these databases will stimulate thedevelopment of computer-aided diagnostic support tools that will become anintegral part of modern medicine. 相似文献
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Hung-Hsin Chen Douglas M. Shaw Lauren E. Petty Misa Graff Ryan J. Bohlender Hannah G. Polikowsky Xue Zhong Daeeun Kim Victoria L. Buchanan Michael H. Preuss Megan M. Shuey Ruth J.F. Loos Chad D. Huff Nancy J. Cox Julie A. Bastarache Lisa Bastarache Kari E. North Jennifer E. Below 《American journal of human genetics》2021,108(1):194-201
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Thomas W. McDade Molly W. Metzger Laura Chyu Greg J. Duncan Craig Garfield Emma K. Adam 《Proceedings. Biological sciences / The Royal Society》2014,281(1784)
Chronic inflammation is a potentially important physiological mechanism linking early life environments and health in adulthood. Elevated concentrations of C-reactive protein (CRP)—a key biomarker of inflammation—predict increased cardiovascular and metabolic disease risk in adulthood, but the developmental factors that shape the regulation of inflammation are not known. We investigated birth weight and breastfeeding duration in infancy as predictors of CRP in young adulthood in a large representative cohort study (n = 6951). Birth weight was significantly associated with CRP in young adulthood, with a negative association for birth weights 2.8 kg and higher. Compared with individuals not breastfed, CRP concentrations were 20.1%, 26.7%, 29.6% and 29.8% lower among individuals breastfed for less than three months, three to six months, 6–12 months and greater than 12 months, respectively. In sibling comparison models, higher birth weight was associated with lower CRP for birth weights above 2.5 kg, and breastfeeding greater than or equal to three months was significantly associated with lower CRP. Efforts to promote breastfeeding and improve birth outcomes may have clinically relevant effects on reducing chronic inflammation and lowering risk for cardiovascular and metabolic diseases in adulthood. 相似文献
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ABSTRACTThe electronic health record (EHR) contains rich histories of clinical care, but has not traditionally been mined for information related to sleep habits. Here, we performed a retrospective EHR study based on a cohort of 3,652 individuals with self-reported sleep behaviors documented from visits to the sleep clinic. These individuals were obese (mean body mass index 33.6 kg/m2) and had a high prevalence of sleep apnea (60.5%), however we found sleep behaviors largely concordant with prior prospective cohort studies. In our cohort, average wake time was 1 hour later and average sleep duration was 40 minutes longer on weekends than on weekdays (p < 10?12). Sleep duration varied considerably as a function of age and tended to be longer in females and in whites. Additionally, through phenome-wide association analyses, we found an association of long weekend sleep with depression, and an unexpectedly large number of associations of long weekday sleep with mental health and neurological disorders (q < 0.05). We then sought to replicate previously published genetic associations with morning/evening preference on a subset of our cohort with extant genotyping data (n = 555). While those findings did not replicate in our cohort, a polymorphism (rs3754214) in high linkage disequilibrium with a previously published polymorphism near TARS2 was associated with long sleep duration (p < 0.01). Collectively, our results highlight the potential of the EHR for uncovering the correlates of human sleep in real-world populations. 相似文献
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Deciphering the genetic basis of human diseases is an important goal of biomedical research. On the basis of the assumption that phenotypically similar diseases are caused by functionally related genes, we propose a computational framework that integrates human protein–protein interactions, disease phenotype similarities, and known gene–phenotype associations to capture the complex relationships between phenotypes and genotypes. We develop a tool named CIPHER to predict and prioritize disease genes, and we show that the global concordance between the human protein network and the phenotype network reliably predicts disease genes. Our method is applicable to genetically uncharacterized phenotypes, effective in the genome‐wide scan of disease genes, and also extendable to explore gene cooperativity in complex diseases. The predicted genetic landscape of over 1000 human phenotypes, which reveals the global modular organization of phenotype–genotype relationships. The genome‐wide prioritization of candidate genes for over 5000 human phenotypes, including those with under‐characterized disease loci or even those lacking known association, is publicly released to facilitate future discovery of disease genes. 相似文献
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Syaron Basnet Ilona Merikanto Tuuli Lahti Satu Männistö Tiina Laatikainen Erkki Vartiainen 《Chronobiology international》2017,34(4):462-470
Chronotype is an emerging predictor of health and longevity, and understanding its influence on chronic diseases is important for constructing conceptual models of long-term pathways to health. We assessed the associations of chronotype with health status in the general Finnish adult population. Our population-based data were derived from the National FINRISK 2012 study and consisted of 4414 participants, aged 25–74?years, living in Finland. As part of their health examination, participants were asked about their circadian preference to the daily activities (morningness–eveningness) and a diagnosis or treatment for a set of common noncommunicable medical conditions and chronic diseases during the past 12?months. We found that there were 1935 (43.8%) morning types (MTs) and 595 (13.5%) evening types (ETs) and that 1884 (42.7%) were intermediates. As compared with the MTs, the ETs had significantly greater odds for depression (OR = 2.44, 95% CI = 1.52–3.90, p < 0.001) and other mental disorders (OR = 5.18, 95% CI = 2.32–11.52, p < 0.001). The odds were also increased for gallstones, and chronic obstructive pulmonary disease, but these did not remain significant after controlling for multiple testing. Responses to the single-item subjective estimation on the chronotype yielded the association of the definitely evening type of persons with the diagnosis or treatment of cardiac insufficiency (OR = 1.99, 95% CI = 1.02–3.88, p = 0.044) that was corroborated as the greater the eveningness score was, the more common the diagnosis or treatment of cardiac insufficiency was (β = 0.92, 95% CI = 0.85–0.98, p = 0.013). This exploratory study adds further support to the role of evening chronotype in chronic disease risk, albeit underlying mechanisms remain to be elucidated. 相似文献
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A sustainable human population (e.g., range, density, and total numbers) is essential to health and in management. The notion of sustainability applies to all species and ecosystems and to the biosphere. Sustainability involves the health not only of individual humans, but also of ecosystems and other species. Thus, sustainability of the human population is important because of the wealth of factors involved: both the elements of systems it affects and those that contribute to its size. In this article, I address the sustainability of the human population on the basis of the argument that other species serve as examples of sustainability at the species level—an example of an application of systemic management that simultaneously accounts for complexity and achieves measurable health for individuals, species, and ecosystems. I conclude that the human population is two to four orders of magnitude larger than is optimally sustainable when compared with the populations of other mammalian species of similar body size and that this is a significant contributor to health problems for our species, other species, and ecosystems—a systemic pathology. 相似文献
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Robert R. Dunn T. Jonathan Davies Nyeema C. Harris Michael C. Gavin 《Proceedings. Biological sciences / The Royal Society》2010,277(1694):2587-2595
The differences in the richness and prevalence of human pathogens among different geographical locations have ramifying consequences for societies and individuals. The relative contributions of different factors to these patterns, however, have not been fully resolved. We conduct a global analysis of the relative influence of climate, alternative host diversity and spending on disease prevention on modern patterns in the richness and prevalence of human pathogens. Pathogen richness (number of kinds) is largely explained by the number of birds and mammal species in a region. The most diverse countries with respect to birds and mammals are also the most diverse with respect to pathogens. Importantly, for human health, the prevalence of key human pathogens (number of cases) is strongly influenced by disease control efforts. As a consequence, even where disease richness is high, we might still control prevalence, particularly if we spend money in those regions where current spending is low, prevalence is high and populations are large. 相似文献
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Gillian M. Belbin Sinead Cullina Stephane Wenric Emily R. Soper Benjamin S. Glicksberg Denis Torre Arden Moscati Genevieve L. Wojcik Ruhollah Shemirani Noam D. Beckmann Ariella Cohain Elena P. Sorokin Danny S. Park Jose-Luis Ambite Steve Ellis Adam Auton Eimear E. Kenny 《Cell》2021,184(8):2068-2083.e11
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人巨细胞病毒中枢神经系统先天性感染小鼠模型的电镜研究 总被引:1,自引:0,他引:1
目的 应用人巨细胞病毒(HCMV)建立先天性中枢神经系统感染小鼠模型。以电镜研究探讨HCMV先天性感染对中枢神经系统损伤的机制和程度。方法 将HCMV腹腔内中纯系6-8周龄Balb/c雌雄小鼠成功后给予酱受孕,待雌鼠临产时取出胎鼠脑双侧大脑皮层,进行病毒分离、病理学检验和电镜研究。结果 在鼠脑组织上清液中分离出HCMV;病理学证实,鼠脑为侵袭性脑膜脑炎性病理改变;电镜下研究,在感染组子代鼠脑组织血 相似文献
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Charles K. Minns 《Journal of Aquatic Ecosystem Stress and Recovery (Formerly Journal of Aquatic Ecosystem Health)》1995,4(1):1-24
Rising concern for the future of humans and the earth's ecosystems provides the backdrop for an essay on approaches to assessing and managing ecosystem health. A review and critique of two rival metaphors of human health, illness and wellness, provide the staring point for evaluation of parallel approaches to the assessment and management of ecosystems. The limitations of the metaphors are noted for humans and ecosystems. The impact assessment and ecosystem approach concepts of ecosystem assessment and management are contrasted. As a case history, the nature and pace of change in the Bay of Quinte ecosystem are reviewed, spanning from colonization by the Empire Loyalists at the end of the 18th century through the current development of a remedial action plan for the ecosystem. The review includes the long-term scientific study of the Bay's response to point-source phosphorus control (Project Quinte) and the recent efforts to develop and implement a coordinated clean-up program (Remedial Action Plan). From the lessons of the Quinte experience, a framework is derived, combining the illness and wellness approaches to health. The framework deals with five topics: uncertainty and the precautionary principle; an ecosystem health scale; indicators of ecosystem health; maximum allowable change; and, regulation and planning. Uncertainty should not be used to justify inaction. A precautionary principle assumes that impacts will occur and places the burden of proof on the proponents of ecosystem disturbance. An ecosystem health scale is defined using current, original, and potential conditions. Restoration to the original condition is unlikely but provides a justifiable direction for actions to establish sustainability. Indicators of ecosystem health with sustainable ranges are preferred over end-points and thresholds. The concept of maximum allowable change is promoted with a tentative suggestion that a fifty percent rule might be used. Finally, an argument for the combined use of regulation and planning. Regulatory approaches tend to perpetuate confrontation. Planning can be used to lengthen the time-horizon from quarterly reports to generations and identify self-regulating codes of behaviour. The framework is briefly discussed and placed in a broader context linking humans and ecosystem, illness and wellness.Based on the text of a talk presented at the Cumulative Impact Assessment Workshop held in Toronto, Ontario, December 1992, and sponsored by the North Central Division of the American Fisheries Society. 相似文献