Novartis Foundation Symposium最新文献_第6页

Gene-environment interaction in complex diseases: asthma as an illustrative case. 复杂疾病中的基因-环境相互作用:以哮喘为例。

Novartis Foundation Symposium Pub Date : 2008-08-12 DOI: 10.1002/9780470696781.CH15

F. Martinez

引用次数: 24

Introduction: whither gene-environment interactions? 引言:基因与环境的相互作用走向何方?

Novartis Foundation Symposium Pub Date : 2008-08-12 DOI: 10.1002/9780470696781.CH1

M. Rutter

引用次数: 8

Use of monozygotic twins to investigate the relationship between 5HTTLPR genotype, depression and stressful life events: an application of Item Response Theory. 应用项目反应理论，利用同卵双胞胎研究5HTTLPR基因型与抑郁和应激性生活事件的关系。

Novartis Foundation Symposium Pub Date : 2008-08-12 DOI: 10.1002/9780470696781.CH4

N. Wray, W. Coventry, M. James, G. Montgomery, L. Eaves, N. Martin

{"title":"Use of monozygotic twins to investigate the relationship between 5HTTLPR genotype, depression and stressful life events: an application of Item Response Theory.","authors":"N. Wray, W. Coventry, M. James, G. Montgomery, L. Eaves, N. Martin","doi":"10.1002/9780470696781.CH4","DOIUrl":"https://doi.org/10.1002/9780470696781.CH4","url":null,"abstract":"We examine the interaction between stressful life events (SLE) and genotypes for the length polymorphism of the serotonin receptor gene (5HTTLPR) on risk of depression. We hypothesize that if the interaction is real, monozygotic twin pairs (MZT) homozygous for the short allele (SS) will have a greater within pair variance in depression measures than MZT homozygous for the long allele (LL), as a reflection of their increased sensitivity to unknown environmental risk factors. Telephone interviews were used to assess symptoms of depression and suicidality on 824 MZT. Rather than using the interview items to calculate sum scores or allocate diagnostic classes we use Item Response Theory to model the contribution of each item to each individual's underlying liability to depression. SLE were also measured on the MZT assessed by mailed questionnaire on average 3.8 years previously, and these were used in follow-up analyses. We find no evidence for significant differences in within pair variance between 5HTTLPR genotypic classes and so can provide no support for interaction between these genotypes and the environment. The use of MZT provides a novel framework for examining genotype x environment interaction in the absence of measures on SLE.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"17 2","pages":"48-59; discussion 59-70"},"PeriodicalIF":0.0,"publicationDate":"2008-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50674311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 22

Unbiased forward genetics and systems biology approaches to understanding how gene-environment interactions work to predict susceptibility and outcomes of infections. 无偏见的正向遗传学和系统生物学方法，了解基因-环境相互作用如何预测易感性和感染的结果。

Novartis Foundation Symposium Pub Date : 2008-08-12 DOI: 10.1002/9780470696781.CH12

M. Kotb, Nourtan Fathey, R. Aziz, Sarah Rowe, Robert W. Williams, Lu Lu

{"title":"Unbiased forward genetics and systems biology approaches to understanding how gene-environment interactions work to predict susceptibility and outcomes of infections.","authors":"M. Kotb, Nourtan Fathey, R. Aziz, Sarah Rowe, Robert W. Williams, Lu Lu","doi":"10.1002/9780470696781.CH12","DOIUrl":"https://doi.org/10.1002/9780470696781.CH12","url":null,"abstract":"Like most human diseases, infectious diseases are effected by complex genetic traits and multiple, interactive environmental and inherent host factors. By linking specific genotypes to disease susceptibility phenotypes we can identify the genetic basis for inter-individual differences in disease susceptibility as well as gain insight into how gene-environment interactions influence infection outcomes. Our research has focused on delineating interactive pathways and molecular events modulating host resistance or susceptibility to specific pathogens. Our model system has been that of Group A Streptococcus infections that can manifest in starkly different ways and cause distinct diseases in genetically distinct individuals. We have extended our work to other pathogens, including those with a potential of causing major, global biological threats. In as much as it is quite difficult to conduct certain infectious disease studies in humans, there has been a critical need for small animal models for infectious diseases. Appreciating the limitations of existing models, we developed several novel and complementary mouse models that are ideal for use in systems genetics studies of complex diseases. These models not only allow biological validation of known genetic associations, but importantly they afford an unbiased tool for discovering novel genes and pathways contributing to disease outcomes, under different environments.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"20 3","pages":"156-65; discussion 165-7, 181-3"},"PeriodicalIF":0.0,"publicationDate":"2008-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50674390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Gene-environment interaction: overcoming methodological challenges. 基因-环境相互作用:克服方法论挑战。

Novartis Foundation Symposium Pub Date : 2008-08-12 DOI: 10.1002/9780470696781.CH2

R. Uher

{"title":"Gene-environment interaction: overcoming methodological challenges.","authors":"R. Uher","doi":"10.1002/9780470696781.CH2","DOIUrl":"https://doi.org/10.1002/9780470696781.CH2","url":null,"abstract":"While interacting biological effects of genes and environmental exposures (G x E) form a natural part of the causal framework underlying disorders of human health, the detection of G x E relies on inference from statistical interactions observed at population level. The validity of such inference has been questioned because the presence or absence of statistical interaction depends on measurement scale and statistical model. Furthermore, the feasibility of G x E research is threatened by the fact that tests of statistical interaction require large samples and their power is substantially reduced by unreliability in the assessments of genes, environmental exposures and pathology. It is demonstrated that concerns about statistical models and scaling can be addressed by integration of observational and experimental data. Judicious selection of genes and environmental factors should limit multiple testing. To overcome the challenge of low statistical power, it is suggested to maximize the reliability of measurement, integrate prior knowledge under Bayesian framework and facilitate pooling of data across studies by use of standardized stratified reporting. Consistencies and discrepancies among studies can be exploited for methodological analysis and model specification.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"26 7","pages":"13-26; discussion 26-30, 68-70"},"PeriodicalIF":0.0,"publicationDate":"2008-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50674122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 28

Pancreatic pathology in type 1 diabetes in human. 人类1型糖尿病的胰腺病理。

Novartis Foundation Symposium Pub Date : 2008-08-12 DOI: 10.1002/9780470697405.CH2

A. Foulis

{"title":"Pancreatic pathology in type 1 diabetes in human.","authors":"A. Foulis","doi":"10.1002/9780470697405.CH2","DOIUrl":"https://doi.org/10.1002/9780470697405.CH2","url":null,"abstract":"In type 1 autoimmune diabetes there is a selective destruction of insulin-secreting beta cells. Around the time of clinical presentation, insulitis, a chronic inflammatory infiltrate of the islets affecting primarily insulin containing islets, is present in the majority of cases. The inflammatory infiltrate consists primarily of T lymphocytes; CD8 cells outnumber CD4 cells, there are fewer B lymphocytes and macrophages are relatively scarce. beta cell death may involve the Fas apoptotic pathway since they have been shown to express Fas, infiltrating T lymphocytes express Fas-L and apoptotic beta cells have been described. Hyperexpression of class I MHC by all the endocrine cells in many insulin-containing islets is a well recognized phenomenon, characteristic of the disease. It has been argued that this is an earlier event than insulitis within a given islet and appears to be due to secretion of interferon alpha by beta cells within that islet. A recent study has found evidence of Coxsackie virus infection in beta cells in three out of six pancreases of patients with recent-onset type 1 diabetes. Coxsackie viruses are known to induce interferon alpha secretion by beta cells and this could initiate the sequence of events that culminates in their autoimmune destruction.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"22 9","pages":"2-13; discussion 13-8, 122-9, 202-3"},"PeriodicalIF":0.0,"publicationDate":"2008-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/9780470697405.CH2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50674544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 26

Practice and public policy in the era of gene-environment interactions. 基因-环境相互作用时代的实践与公共政策。

Novartis Foundation Symposium Pub Date : 2008-08-12 DOI: 10.1002/9780470696781.CH7

K. Dodge

{"title":"Practice and public policy in the era of gene-environment interactions.","authors":"K. Dodge","doi":"10.1002/9780470696781.CH7","DOIUrl":"https://doi.org/10.1002/9780470696781.CH7","url":null,"abstract":"This chapter argues that implications of the gene-environment interaction revolution for public policy and practice are contingent on how the findings get framed in public discourse. Frame analysis is used to identify the implications of the ways in which findings are cast. The frame of 'defective group' perpetuates racial and class stereotypes and limits policy efforts to redress health disparities. Furthermore, empirical evidence finds it inaccurate. The frame of'defective gene' precludes the adaptive genetic significance of genes. The frame of 'individual genetic profile' offers individualized health care but risks misapplication in policies that place responsibility for disease prevention on the individual to the policy relief of industry and toxic environments. Framing the interaction in terms of 'defective environments' promotes the identification of harmful environments that can be regulated through policy. The 'therapeutic environment' frame offers hope of discovering interventions that have greater precision and effectiveness but risks dis-incentivizing the pharmaceutical industry from discovering drug treatments for 'obscure' gene-environment match groups. Can a more accurate and helpful framing of the gene-environment interaction be identified? Findings that genes shape environments and that environments alter the gene pool suggest a more textured and symbiotic relationship that is still in search of an apt public framing.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"28 5","pages":"87-97; discussion 97-102, 122-7"},"PeriodicalIF":0.0,"publicationDate":"2008-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50674172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Role of gene-stress interactions in gene-finding studies. 基因-应激相互作用在基因发现研究中的作用。

Novartis Foundation Symposium Pub Date : 2008-03-01 DOI: 10.1002/9780470696781.CH6

H. Snieder, Xiaoling Wang, V. Lagou, B. Penninx, H. Riese, C. Hartman

{"title":"Role of gene-stress interactions in gene-finding studies.","authors":"H. Snieder, Xiaoling Wang, V. Lagou, B. Penninx, H. Riese, C. Hartman","doi":"10.1002/9780470696781.CH6","DOIUrl":"https://doi.org/10.1002/9780470696781.CH6","url":null,"abstract":"Identification of genetic variants underlying common complex traits and diseases can be viewed as a three-stage process that jump-started with the sequencing of the human genome. The second phase, characterization of genetic variants in different human populations, has shown major progress in recent years. The increased availability of single nucleotide polymorphisms (SNPs) has already spawned two important developments in genetic association studies. Increasingly, rather than focusing on one or two functional SNPs, candidate gene studies consider all variants within the gene jointly. The second development is that of the whole genome association study. This chapter illustrates two distinct ways in which gene-stress interactions may aid such gene finding studies. We have recently shown for heart rate variability--an index of autonomic dysfunction related to both psychopathology and cardiovascular disease--that exposure to an acute stressful challenge in a standardized lab setting may produce a more heritable endophenotype, facilitating identification of underlying genes. The second example shows how the creation of a cumulative index of chronic stress based on multiple questionnaire- and interview-based measures of stress exposure may be applied in a genome-wide association study of (high) blood pressure to find genes that only come to expression in stressful environments. We conclude that investigation ofgene-environment interactions in the context of both gene- and genome-wide association studies may offer important advantages in gene finding efforts for complex traits and diseases.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"14 2","pages":"71-82; discussion 83-6, 122-7"},"PeriodicalIF":0.0,"publicationDate":"2008-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50674406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

The chaperone function: meanings and myths. 伴侣功能:意义和神话。

Novartis Foundation Symposium Pub Date : 2008-01-01 DOI: 10.1002/9780470754030.ch3

Peter A Lund, R John Ellis

引用次数: 4

Extracellular functions of thioredoxin. 硫氧还蛋白的细胞外功能。

Novartis Foundation Symposium Pub Date : 2008-01-01 DOI: 10.1002/9780470754030.ch14

Hajime Nakamura

引用次数: 22