Genometric analysis of quantitative traits

数量性状的基因组分析

• 批准号: 10267090
• 负责人: alexander f wilson
• 金额: $ 146.26万
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10267090
• 关键词: Address; Annual Reports; Cardiovascular system; Case-Control Studies; Collaborations; Computer Simulation; Computer software; Craniosynostosis; DNA Markers; Data; Databases; Dependence; Elements; Extramural Activities; Family; Genetic; Genetic Heterogeneity; Genetic Medicine; Genome; Genomic medicine; Goals; Heritability; Heterogeneity; Human Genetics; Individual; Iowa; Ireland; Justice; Linear Regressions; Linkage Disequilibrium; Luciferases; Measurement; Meta-Analysis; Metabolic; Metabolism; Methodology; Methods; Modeling; Molecular Genetics; NF1 gene; National Human Genome Research Institute; National Institute of Mental Health; Nature; Not Hispanic or Latino; Parents; Patients; Positioning Attribute; Postdoctoral Fellow; Property; Publishing; Quantitative Genetics; Regression Analysis; Reporting; Research; Research Design; Retirement; Sampling; Scientist; Single Nucleotide Polymorphism; Statistical Methods; Structure; Suggestion; Testing; Time; United States National Institutes of Health; Universities; Update; Variant; Vitamin D; Work; base; biobank; clinical phenotype; cohort; college; density; follow-up; genetic analysis; genome wide association study; genome-wide; insight; next generation sequence data; offspring; population based; population stratification; simulation; software development; statistics; trait; volunteer; web site

SUMMARY Administrative Note The number of ongoing projects, and the number of intramural and extramural collaborators has been substantially reduced because of Dr. Wilsons upcoming retirement in September 2020. The focus of the Genometrics Section over the past year has been to complete ongoing collaborations. Effort has been focused on winding down the current research portfolio. This is the final annual report for the Genometric Analysis of Quantitative Traits project. The last post-doctoral IRTA fellow, Dr. Jeremy Sabourin has taken a position with Biostat Solutions in Frederick, MD. The Staff Scientists in the Genometrics Section have been placed in other equivalent positions at NIH. Dr. Heejong Sung has moved to the National Institute of Mental Health under the direction of Dr. Francis McMahon. Dr. Cristina Justice and Alexa Sorant remain in NHGRI; Dr. Justice under the direction of Dr. Philip Shaw, and Ms. Sorant under the direction of Dr. Joan Bailey-Wilson. Dr. Wilson will continue, part-time, as a special volunteer, or if approved, as an Emeritus Scientist. Software Development Final versions of three projects are now available. In the first, the tiled regression methodology was updated in the Tiled Regression Analysis Package (TRAP). Version 2.0 of TRAP includes additional penalized regression models and is available on the NHGRI website: http://research.nhgri.nih.gov/software/TRAP. In the second project, a faster version of TRAP for quantitative traits (TR-Quant) is now available at https://research.nhgri.nih.gov/software/TRQUANT. And, in the third, software for ComPaSS-GWAS Sabourin et al. 2019 is now available at https://research.nhgri.nih.gov/software/compass-gwas. This version of ComPaSS-GWAS is limited to analysis with PLINK. Collaborations Craniosynostosis As part of an ongoing collaboration with Dr. Simeon Boyd (UC Davis) and Dr. Paul Romiti (U of Iowa) Justice et al. 2012 reported a genome-wide association study (GWAS) for sagittal non-syndromic craniosynostosis (sNCS). This same approach was applied to 215 non-Hispanic parent-offspring trios with metopic non-syndromic craniosynostosis (mNCS). Six variants were identified that were genome-wide significant and one of the variants was replicated in an independent non-Hispanic white sample of 194 unrelated mNCS cases and 333 unaffected controls. A meta-analysis of SNPs common to both the mNCS and sNCS studies identified a single SNP at the genome-wide association suggestive level of 1x10-5. Results from a luciferase studies suggested that a fragment which encompasses this SNP acts as a repressor element. This work was recently published in Human Genetics. Measurement of caf-au-lait macules in NF1 patients. As part of an ongoing collaboration with Dr. Douglas Stewart (NCI), a follow-up to our genome-wide association study of modifiers for a genome-wide association analysis was performed focusing on the number of caf-au-lait macules (CALM) as a clinical phenotype modifying NF1. A borderline genome-wide significant association was identified in the discovery cohort. This association was not replicated in the second cohort and a meta-analysis did not show significantly associated variants with this variant. However, a significant corroboration score (0.72) was obtained for this SNP in the discovery cohort using Complementary Pairs Stability Selection (ComPaSS-GWAS) analysis Sabourin, 2019 suggesting that the lack of replication may be due to heterogeneity of the cohorts rather than type I error. This work is in press in Molecular Genetic and Genomic Medicine 2020. Other ongoing collaborations 1) The ClinSeq project (Les Biesecker, NIH/NHGRI) 2) Statistical properties of fixed and mixed effects models. Dr. Ruzong Fan, Georgetown University. 3) Genetics of traits related to vitamin D metabolism. Dr. Larry Brody, NHGRI, Dr. Barry Shane, Dr. Faith Pangilinan (Trinity College, Ireland). 4) Cardiovascular and metabolic traits in non-Europeans in the UK BioBank database (Dr. Teri Manolio, NHGRI).

概括 行政注释 由于 Wilson 博士即将于 2020 年 9 月退休，正在进行的项目数量以及校内和校外合作者的数量已大幅减少。基因组学部门过去一年的重点是完成正在进行的合作。 工作重点是逐步缩减当前的研究组合。 这是数量性状基因组分析项目的最终年度报告。 最后一位 IRTA 博士后研究员 Jeremy Sabourin 博士已在马里兰州弗雷德里克的 Biostat Solutions 任职。 基因组学部门的科学家已被安排到 NIH 的其他同等职位。 Heejong Sung 博士已在 Francis McMahon 博士的指导下转到国家心理健康研究所。 Cristina Justice 博士和 Alexa Sorant 仍留在 NHGRI； Justice 博士在 Philip Shaw 博士的指导下，Sorant 女士在 Joan Bailey-Wilson 博士的指导下。 威尔逊博士将继续兼职，作为一名特殊志愿者，或者如果获得批准，作为一名名誉科学家。 软件开发 三个项目的最终版本现已推出。 首先，在平铺回归分析包 (TRAP) 中更新了平铺回归方法。 TRAP 2.0 版包括额外的惩罚回归模型，可在 NHGRI 网站上获取：http://research.nhgri.nih.gov/software/TRAP。 在第二个项目中，用于数量性状的 TRAP (TR-Quant) 的更快版本现已在 https://research.nhgri.nih.gov/software/TRQUANT 上提供。 第三个是 ComPaSS-GWAS Sabourin 等人的软件。 2019 年现已在 https://research.nhgri.nih.gov/software/compass-gwas 上提供。 此版本的 ComPaSS-GWAS 仅限于使用 PLINK 进行分析。 合作 颅缝早闭 作为与 Simeon Boyd 博士（加州大学戴维斯分校）和 Paul Romiti 博士（爱荷华大学）Justice 等人持续合作的一部分。 2012 年报道了矢状位非综合征性颅缝早闭 (sNCS) 的全基因组关联研究 (GWAS)。 同样的方法也适用于 215 名患有异位非综合征性颅缝早闭 (mNCS) 的非西班牙裔亲子三人组。 鉴定出 6 个在全基因组范围内具有显着性的变异，其中一个变异在 194 名不相关 mNCS 病例和 333 名未受影响的对照的独立非西班牙裔白人样本中进行了复制。 对 mNCS 和 sNCS 研究共有的 SNP 进行荟萃分析，确定了全基因组关联建议水平为 1x10-5 的单个 SNP。 荧光素酶研究的结果表明，包含该 SNP 的片段充当阻遏元件。 这项工作最近发表在《人类遗传学》上。 NF1 患者中咖啡斑的测量。 作为与 Douglas Stewart 博士 (NCI) 持续合作的一部分，我们对全基因组关联分析修饰因子进行了后续研究，重点关注作为修饰 NF1 临床表型的咖啡斑 (CALM) 数量。 在发现队列中发现了临界全基因组显着关联。 这种关联没有在第二组中重复，并且荟萃分析没有显示与该变体显着相关的变体。 然而，使用互补对稳定性选择 (ComPaSS-GWAS) 分析 Sabourin, 2019 在发现队列中获得了该 SNP 的显着佐证分数 (0.72)，表明缺乏复制可能是由于队列的异质性而不是 I 型错误。 这项工作正在《分子遗传学和基因组医学 2020》上发表。 其他正在进行的合作 1) ClinSeq 项目（Les Biesecker，NIH/NHGRI） 2）固定效应模型和混合效应模型的统计特性。 范汝宗博士，乔治城大学。 3）维生素D代谢相关性状的遗传学。 Larry Brody 博士，NHGRI，Barry Shane 博士，Faith Pangilinan 博士（爱尔兰三一学院）。 4) 英国生物银行数据库中非欧洲人的心血管和代谢特征（Teri Manolio 博士，NHGRI）。

项目成果

Informatics and genetic epidemiology.

信息学和遗传流行病学。

• 发表时间: 2014
• 期刊: Methods of information in medicine
• 影响因子: 1.7
• 作者: Ziegler,A;Wilson,AF;Gagnon,F
• 通讯作者: Gagnon,F

Heritability of quantitative traits associated with type 2 diabetes mellitus in large multiplex families from South India.

• DOI: 10.1016/j.metabol.2009.04.041
• 发表时间: 2009-10
• 期刊: METABOLISM-CLINICAL AND EXPERIMENTAL
• 影响因子: 9.8
• 作者: Mathias, Rasika A.;Deepa, Mohan;Deepa, Raj;Wilson, Alexander F.;Mohan, Vishwanathan
• 通讯作者: Mohan, Vishwanathan

Genetic associations with childhood brain growth, defined in two longitudinal cohorts.

• DOI: 10.1002/gepi.22122
• 发表时间: 2018-06
• 期刊: Genetic epidemiology
• 影响因子: 2.1
• 作者: Szekely E;Schwantes-An TL;Justice CM;Sabourin JA;Jansen PR;Muetzel RL;Sharp W;Tiemeier H;Sung H;White TJ;Wilson AF;Shaw P
• 通讯作者: Shaw P