MODELS FOR THE GENETIC EPIDEMIOLOGY OF CHRONIC DISEASE

慢性病遗传流行病学模型

• 批准号: 7603101
• 负责人: SANDRA J HASSTEDT
• 金额: $ 19.27万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-15 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603101
• 关键词: Affect; Chronic Disease; Communities; Complex; Computer software; Computers; Data; Data Analyses; Development; Disease; Environment; Environmental Risk Factor; Family; Funding; Genes; Genetic Models; Genotype; Imagery; Java; Linkage Disequilibrium; Markov Chains; Memory; Methodology; Methods; Modeling; Monte Carlo Method; Pharmaceutical Preparations; Play; Probability; Procedures; Research; Research Personnel; Role; Sampling; Source Code; Speed; Time; Writing; disorder risk; genetic analysis; genetic epidemiology; genetic linkage analysis; genetic pedigree; graphical user interface; improved; programs; simulation; trait; usability

DESCRIPTION (provided by applicant): This is a competing continuation application for years 21-25 of a project to develop and implement models and methodology for the likelihood analysis of pedigree data and to distribute the resultant software to the research community. Each aspect of the proposal involves PAP (Pedigree Analysis Package). Parametric genetic analysis, the primary strength of PAP, should play a role in the multi-pronged approach needed to tackle the difficult task of characterizing and localizing genes for complex diseases, which result from complicated interactions of multiple genes and environmental factors. Non-parametric linkage analysis will also become available in PAP upon completion of extensions proposed in this application. Although there exist a number of other software packages for the analysis of family data, none matches the versatility of PAP. The extension of PAP more efficiently produces software for diverse genetic analysis than does the development of new software for that purpose. In addition, PAP has a track record for having been wellsupported over the years. During the previous funding period, a graphical user interface in Java was developed to facilitate the use of PAP. During the remaining year of funding the conversion of the source code will be completed, thereby making PAP very portable and convenient to install while maintaining all the analysis versatility. Nevertheless, PAP remains impractical for multipoint linkage analysis, because of the memory and computer time requirements. Therefore, this application proposes to remedy that shortcoming by implementing Markov chain Monte Carlo (MCMC) methods for the analysis of multi-locus marker data. MCMC methods sample, rather than exhaustively enumerate, the possible combinations of genotypes within a pedigree, therefore effecting an enormous saving of computer time. With the availability of MCMCproduced probabilities, multipoint linkage analysis will become feasible for either variance components models or using any of the extensive selection of major gene models already available in PAP. Nevertheless, the current application also proposes to develop new genetic models of disease risk, including a mode-of-inheritance free method. In addition, this application proposes to implement changes to increase computational speed, allow data exploration, and facilitate data handling and analysis, while continuing to distribute and support PAP.

描述（由申请人提供）：这是一个为期 21-25 年的竞争性延续申请，旨在开发和实施用于谱系数据可能性分析的模型和方法，并将生成的软件分发给研究界。该提案的每个方面都涉及 PAP（谱系分析包）。参数遗传分析是 PAP 的主要优势，应该在解决复杂疾病基因特征和定位的艰巨任务所需的多管齐下的方法中发挥作用，这些疾病是由多个基因和环境因素的复杂相互作用造成的。在完成本申请中提出的扩展后，非参数连锁分析也将在 PAP 中可用。尽管存在许多其他用于分析家庭数据的软件包，但没有一个能与 PAP 的多功能性相匹配。 PAP 的扩展比为此目的开发新软件更有效地生产用于多种遗传分析的软件。此外，人民行动党多年来一直得到良好支持。在上一个资助期间，开发了 Java 图形用户界面以方便 PAP 的使用。在资助的剩余一年内，将完成源代码的转换，从而使 PAP 非常便携且易于安装，同时保持所有分析的多功能性。然而，由于内存和计算机时间的要求，PAP 对于多点链接分析仍然不切实际。因此，本申请提出通过实施马尔可夫链蒙特卡罗（MCMC）方法来分析多位点标记数据来弥补该缺点。 MCMC 方法对谱系中可能的基因型组合进行抽样，而不是详尽地列举，因此可以节省大量计算机时间。随着 MCMC 产生的概率的可用性，多点连锁分析对于方差分量模型或使用 PAP 中现有的任何主要基因模型的广泛选择都将变得可行。尽管如此，当前的申请还建议开发新的疾病风险遗传模型，包括无遗传模式的方法。此外，该应用程序建议实施更改以提高计算速度、允许数据探索并促进数据处理和分析，同时继续分发和支持 PAP。

项目成果

Effect of the peroxisome proliferator-activated receptor-gamma 2 pro(12)ala variant on obesity, glucose homeostasis, and blood pressure in members of familial type 2 diabetic kindreds.

过氧化物酶体增殖物激活受体-γ 2 pro(12)ala 变体对 2 型糖尿病家族成员的肥胖、葡萄糖稳态和血压的影响。

• DOI: 10.1210/jcem.86.2.7205
• 发表时间: 2001
• 期刊: The Journal of clinical endocrinology and metabolism.
• 作者: Hasstedt,SJ;Ren,QF;Teng,K;Elbein,SC
• 通讯作者: Elbein,SC

Polymorphisms in the NPY2R gene show significant associations with BMI that are additive to FTO, MC4R, and NPFFR2 gene effects.

• DOI: 10.1038/oby.2011.239
• 发表时间: 2011-11
• 期刊: OBESITY
• 影响因子: 6.9
• 作者: Hunt, Steven C.;Hasstedt, Sandra J.;Xin, Yuanpei;Dalley, Brian K.;Milash, Brett A.;Yakobson, Emanuel;Gress, Richard E.;Davidson, Lance E.;Adams, Ted D.
• 通讯作者: Adams, Ted D.

Variance components/major locus likelihood approximation for quantitative, polychotomous, and multivariate data.

定量、多分类和多变量数据的方差分量/主轨迹似然近似。

• DOI: 10.1002/gepi.1370100302
• 发表时间: 1993
• 期刊: Genetic epidemiology
• 影响因子: 2.1
• 作者: Hasstedt,SJ

Effects of household sharing on high density lipoprotein and its subfractions.

家庭共享对高密度脂蛋白及其亚组分的影响。

• DOI: 10.1002/gepi.1370020403
• 发表时间: 1985
• 期刊: Genetic epidemiology
• 影响因子: 2.1
• 作者: Hasstedt,SJ;Kuida,H;Ash,KO;Williams,RR
• 通讯作者: Williams,RR

Hereditary Thrombophilia as a Model for Multigenic Disease

• DOI: 10.1055/s-0037-1615894
• 发表时间: 1999-08
• 期刊: Thrombosis and Haemostasis
• 影响因子: 6.7
• 作者: E. Bovill;S. Hasstedt;M. Leppert;G. Long