Computational Methods to Detect Epistasis
检测上位性的计算方法
基本信息
- 批准号:7468452
- 负责人:
- 金额:$ 12.87万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-07-10 至 2010-06-30
- 项目状态:已结题
- 来源:
- 关键词:AccountingAlcoholismAsthmaAwardBiologicalBiological MarkersCollaborationsComplexComputer SimulationComputing MethodologiesDataData AnalysesData SetDetectionDevelopment PlansDiabetes MellitusDiseaseEducational workshopEffectivenessElevationEpidemiologyEpistatic GeneFailureGenerationsGenesGeneticGenetic EpistasisGenotypeGoalsGrantHeadHuman GenomeKnowledgeLaboratoriesLeadMalignant NeoplasmsMathematicsMeasurementMedicalMental DepressionMentorsMetabolic PathwayMethodologyMethodsModelingMolecular BiologyNumbersPathway interactionsPharmaceutical PreparationsPharmacogeneticsPharmacogenomicsPhenotypePlayPolymorphism AnalysisRateRelative (related person)ResearchResearch PersonnelResearch Project GrantsResearch ProposalsRiskRoleSignal TransductionSimulateSingle Nucleotide PolymorphismSocietiesStatistical MethodsTechniquesTestingTrainingUnited States National Institutes of HealthUniversitiesValidationWarfarinWashingtoncareerclinically relevantdesigndrug metabolismexperiencegene interactiongenetic analysisgenetic linkageinterestmetabolic abnormality assessmentmodels and simulationnoveloptimismoutcome forecastprogramsresponseskillsstatisticssuccesstechnology development
项目摘要
The completion of the draft sequence of the human genome and the continuing development of
technologies to rapidly genotype single nucleotide polymorphisms (SNP) have led to great optimism that
researchers will be able to determine the genetic mechanisms contributing to many common diseases.
However, thus far there has been little success in finding genes to account for the large genetic components
of common, complex diseases such as cancer, diabetes, depression, alcoholism, and asthma.
These complex phenotypes are likely to be associated with gene interactions more complicated than
simple additive or multiplicative models suggest. While great progress had been made on Mendelian
diseases using single-locus models, the failure of these methods to determine the genetic contributors to
many of the common diseases that are so costly to society underscores the need to develop new
methodologies specifically aimed at detecting gene interactions.
The goal of this proposal is to develop and evaluate novel methods for detecting gene-gene (epistatic)
interactions and to apply them to pharmacogenetic data relating to drug metabolism. Specifically, the aims
are: 1) to develop statistical methods to test for epistasis between candidate loci, focusing on methods to
control the loss of power associated with correcting for multiple tests, 2) to evaluate the effectiveness of
these detection and inference methods on simulated data, and 3) to apply and test these methods on real
data from the Pharmacogenetics Research Network project headed by Dr. Howard McLeod at Washington
University in St. Louis (U01 GM63340, Functional Polymorphism Analysis in Drug Pathways) and from
warfarin metabolism studies headed by Dr. Brian Gage, also at Washington University (R01 HL71038 and
R01 HL074724).
Achieving these aims will require, in addition to mathematical skills, both statistical expertise and biological
knowledge of genetics and metabolic pathways supplemented by knowledge of the laboratory techniques
used to generate data for analysis. To this end, the proposed award will supplement Dr. Culverhouse's
previous training in mathematics and epidemiology with training in statistics and molecular biology.
Experience from this period of collaboration, coursework, and mentoring will enable Dr. Culverhouse to play
a leading quantitative role in multi-disciplinary scientific teams.
人类基因组序列草图的完成和
对单核苷酸多态性(SNP)进行快速基因分型的技术已经带来了极大的乐观,
研究人员将能够确定导致许多常见疾病的遗传机制。
然而,到目前为止,在寻找基因来解释大的遗传成分方面几乎没有成功。
癌症、糖尿病、抑郁症、酒精中毒和哮喘等常见的复杂疾病。
这些复杂的表型可能与基因相互作用有关,
简单的加法或乘法模型建议。虽然孟德尔遗传学已经取得了很大的进展,
疾病使用单基因座模型,这些方法的失败,以确定遗传贡献者,
许多对社会造成巨大损失的常见疾病强调了开发新的
专门针对检测基因相互作用的方法。
本提案的目的是开发和评估检测基因-基因(上位性)的新方法
相互作用,并将其应用于药物代谢相关的药物遗传学数据。具体而言,目标
是:1)开发统计方法来测试候选基因座之间的上位性,重点是方法,
控制与校正多个测试相关的功率损失,2)评估
这些检测和推理方法在模拟数据上的应用,以及3)在真实的数据上应用和测试这些方法
来自华盛顿的霍华德麦克劳德博士领导的药物遗传学研究网络项目的数据
圣路易斯大学(U01 GM63340,药物途径中的功能多态性分析)和来自
由Brian Gage博士领导的华法林代谢研究,也在华盛顿大学(R01 HL 71038和
R01 HL074724)。
要实现这些目标,除了数学技能外,还需要统计学和生物学方面的专门知识。
遗传学和代谢途径的知识,辅以实验室技术的知识
用于生成数据进行分析。为此,拟议中的奖项将补充卡尔弗豪斯博士的
以前接受过数学和流行病学培训,并接受过统计学和分子生物学培训。
从这一时期的合作,课程和指导经验将使博士。
在多学科科学团队中发挥领先的定量作用。
项目成果
期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Gene x gene and gene x environment interactions for complex disorders.
基因X基因和基因X环境相互作用,用于复杂疾病。
- DOI:10.1186/1753-6561-1-s1-s72
- 发表时间:2007
- 期刊:
- 影响因子:0
- 作者:Culverhouse R;Hinrichs AL;Jin CH;Suarez BK
- 通讯作者:Suarez BK
The restricted partition method.
- DOI:10.1016/b978-0-12-380862-2.00006-0
- 发表时间:2010
- 期刊:
- 影响因子:0
- 作者:R. Culverhouse
- 通讯作者:R. Culverhouse
Incorporating linkage information into a common disease/rare variant framework.
- DOI:10.1002/gepi.20654
- 发表时间:2011
- 期刊:
- 影响因子:2.1
- 作者:Hinrichs AL;Suarez BK
- 通讯作者:Suarez BK
Linkage and association analyses of principal components in expression data.
表达数据中主成分的连锁和关联分析。
- DOI:10.1186/1753-6561-1-s1-s46
- 发表时间:2007
- 期刊:
- 影响因子:0
- 作者:Hinrichs,AnthonyL;Culverhouse,Robert;Jin,CarolH;Suarez,BrianK
- 通讯作者:Suarez,BrianK
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
ROBERT C CULVERHOUSE其他文献
ROBERT C CULVERHOUSE的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('ROBERT C CULVERHOUSE', 18)}}的其他基金
INTEGRATING GENETICS, ADVERSE EVENTS, AND ADHERENCE TO IMPROVE SMOKING CESSATION
整合遗传学、不良事件和坚持以改善戒烟
- 批准号:
9050661 - 财政年份:2015
- 资助金额:
$ 12.87万 - 项目类别:
DEVELOPING STRATEGIES FOR JOINT GENE-ENVIRONMENT ANALYSIS
制定联合基因-环境分析策略
- 批准号:
8217748 - 财政年份:2011
- 资助金额:
$ 12.87万 - 项目类别:
DEVELOPING STRATEGIES FOR JOINT GENE-ENVIRONMENT ANALYSIS
制定联合基因-环境分析策略
- 批准号:
8330779 - 财政年份:2011
- 资助金额:
$ 12.87万 - 项目类别:
GENETIC INTERACTIONS CONTRIBUTING TO ALCOHOL AND NICOTINE DEPENDENCE
导致酒精和尼古丁依赖的基因相互作用
- 批准号:
7386896 - 财政年份:2008
- 资助金额:
$ 12.87万 - 项目类别:
GENETIC INTERACTIONS CONTRIBUTING TO ALCOHOL AND NICOTINE DEPENDENCE
导致酒精和尼古丁依赖的基因相互作用
- 批准号:
7575172 - 财政年份:2008
- 资助金额:
$ 12.87万 - 项目类别:
相似海外基金
Development and evaluation of a smartphone application to promote the use of alcoholism Self-help groups
开发和评估智能手机应用程序以促进酗酒自助团体的使用
- 批准号:
23K02994 - 财政年份:2023
- 资助金额:
$ 12.87万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
PRECLINICAL MEDICATIONS SCREENING IN DEPENDENCE, AFFECT AND PAIN MODELS OF ALCOHOLISM
酗酒的依赖性、影响和疼痛模型的临床前药物筛选
- 批准号:
10953233 - 财政年份:2023
- 资助金额:
$ 12.87万 - 项目类别:
Fragment-based Discovery of COMT Inhibitors as a Novel Pharmacotherapy for Alcoholism
基于片段的 COMT 抑制剂的发现作为酒精中毒的新型药物疗法
- 批准号:
10667129 - 财政年份:2023
- 资助金额:
$ 12.87万 - 项目类别:
Voicing the Experience of Adolescents in Francophone Narratives of Family Alcoholism
在家庭酗酒的法语叙述中表达青少年的经历
- 批准号:
2778431 - 财政年份:2022
- 资助金额:
$ 12.87万 - 项目类别:
Studentship
ALCOHOLISM SOLUTIONS: SYNTHESIZING INFORMATION TO SUPPORT TREATMENTS (ASSIST 2.0)
酗酒解决方案:综合信息以支持治疗(ASSIST 2.0)
- 批准号:
10717436 - 财政年份:2022
- 资助金额:
$ 12.87万 - 项目类别:
Alcoholism Solutions: Synthesizing Information to Support Treatments (ASSIST 2.0)
酗酒解决方案:综合信息支持治疗 (ASSIST 2.0)
- 批准号:
10716165 - 财政年份:2022
- 资助金额:
$ 12.87万 - 项目类别:
Miserable One Half and Mad the Other: A Graphic History of Alcoholism at The Salutation Pub
一半悲惨,另一半疯狂:致敬酒吧酗酒的图解史
- 批准号:
2623065 - 财政年份:2021
- 资助金额:
$ 12.87万 - 项目类别:
Studentship
Investigating the longitudinal relationship between alcohol use, neurophysiological functioning, and Alzheimer disease biomarkers in the Collaborative Study on the Genetics of Alcoholism
在酒精中毒遗传学合作研究中调查饮酒、神经生理功能和阿尔茨海默病生物标志物之间的纵向关系
- 批准号:
10660983 - 财政年份:2020
- 资助金额:
$ 12.87万 - 项目类别:
Neuroimaging multiple memory processes, glucocorticoids and alcoholism risk
神经影像学多重记忆过程、糖皮质激素和酗酒风险
- 批准号:
9977375 - 财政年份:2020
- 资助金额:
$ 12.87万 - 项目类别:
Multimodal Imaging of Cognitive Control in Individuals with a Family History of Alcoholism
有酗酒家族史的个体认知控制的多模态成像
- 批准号:
10228610 - 财政年份:2020
- 资助金额:
$ 12.87万 - 项目类别: