An evolutionary framework to elucidate and interpret the genetic architecture of complex traits in diverse populations

阐明和解释不同人群复杂性状遗传结构的进化框架

基本信息

  • 批准号:
    10458746
  • 负责人:
  • 金额:
    $ 40.98万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-08-01 至 2026-05-31
  • 项目状态:
    未结题

项目摘要

Project Summary / Abstract Both environmental and genetic factors contribute to disparity in disease risks between populations. The genetic causes of differences between populations are intimately tied to the evolutionary histories of these populations. Therefore, a better incorporation of evolutionary thinking will help explain the disparity among diverse populations today and improve clinical practices and personalized care. To this end, the Chiang Lab will continue to develop an integrative framework combining evolutionary population genetics with genetic epidemiology in humans, utilizing both empirical data analysis and quantitative methods development to better probe into the genetic architecture of complex traits within and between populations. This integrative framework consists of three main foci: (1) the genetic architecture of human complex traits, (2) the demographic history, and (3) the adaptive history of human populations. Research in the first topic informs the genetic consequences on our phenome today, while research in the latter two explains the evolutionary mechanisms through which variation arise within and between human populations. More importantly, research from the Chiang Lab focuses not solely on these topics, but also leverages information on one to inform the other. Within this paradigm, the Chiang Lab will focus on the following three goals over the next five years. First, we will execute a comprehensive genetic research program to address the health disparities in Native Hawaiians. Specifically, we will generate the genomic resources necessary to accelerate genetic research in this population. We will then characterize the demographic history of the Native Hawaiians to illustrate the benefit of conducting genomic studies in understudied populations, perform large-scale meta-analysis in Polynesian populations to identify population- specific alleles associated with diseases prevalent in Native Hawaiians, and engage the Native Hawaiian community for future partnership and collaborations. Second, we will investigate the evolutionary etiology for elevated risk in present-day populations. Using Latino population as an example, we will examine if the elevated risk in childhood leukemia in this population is due to the selective pressure introduced during European contact in the 16th century. Third, we will revolutionize the current concept of genetic relatedness by introducing a new genetic similarity matrix among individuals that incorporates information from the genealogical tree of the population. This matrix will improve the performance of a number of statistical genetic applications, such as heritability estimation and phenotype imputation. While we used Native Hawaiians and Latinos as example populations in this proposal, this integrated framework of genetic epidemiology and evolution will also benefit future research in other understudied ethnic minorities. We are uniquely positioned to achieve these goals because of our expertise in combining population genetic principles with medical genetic analysis and statistical genetic development.
项目摘要/摘要

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Charleston Chiang其他文献

Charleston Chiang的其他文献

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{{ truncateString('Charleston Chiang', 18)}}的其他基金

A genome-wide genealogical framework for statistical and population genetic analysis
用于统计和群体遗传分析的全基因组谱系框架
  • 批准号:
    10658562
  • 财政年份:
    2023
  • 资助金额:
    $ 40.98万
  • 项目类别:
Leveraging the Evolutionary History to Improve Identification of Trait-Associated Alleles and Risk Stratification Models in Native Hawaiians
利用进化历史来改进夏威夷原住民性状相关等位基因的识别和风险分层模型
  • 批准号:
    10689017
  • 财政年份:
    2022
  • 资助金额:
    $ 40.98万
  • 项目类别:
Leveraging the Evolutionary History to Improve Identification of Trait-Associated Alleles and Risk Stratification Models in Native Hawaiians
利用进化历史来改进夏威夷原住民性状相关等位基因的识别和风险分层模型
  • 批准号:
    10365815
  • 财政年份:
    2022
  • 资助金额:
    $ 40.98万
  • 项目类别:
An evolutionary framework to elucidate and interpret the genetic architecture of complex traits in diverse populations - diversity supplement
阐明和解释不同群体复杂性状遗传结构的进化框架 - 多样性补充
  • 批准号:
    10539156
  • 财政年份:
    2021
  • 资助金额:
    $ 40.98万
  • 项目类别:
An evolutionary framework to elucidate and interpret the genetic architecture of complex traits in diverse populations
阐明和解释不同人群复杂性状遗传结构的进化框架
  • 批准号:
    10624515
  • 财政年份:
    2021
  • 资助金额:
    $ 40.98万
  • 项目类别:
An evolutionary framework to elucidate and interpret the genetic architecture of complex traits in diverse populations
阐明和解释不同人群复杂性状遗传结构的进化框架
  • 批准号:
    10640193
  • 财政年份:
    2021
  • 资助金额:
    $ 40.98万
  • 项目类别:
An evolutionary framework to elucidate and interpret the genetic architecture of complex traits in diverse populations
阐明和解释不同人群复杂性状遗传结构的进化框架
  • 批准号:
    10727037
  • 财政年份:
    2021
  • 资助金额:
    $ 40.98万
  • 项目类别:
An evolutionary framework to elucidate and interpret the genetic architecture of complex traits in diverse populations
阐明和解释不同人群复杂性状遗传结构的进化框架
  • 批准号:
    10275367
  • 财政年份:
    2021
  • 资助金额:
    $ 40.98万
  • 项目类别:
Using whole genomes to study demography and mapping power of a population isolate
使用全基因组研究人口统计学和群体隔离的绘图能力
  • 批准号:
    8527468
  • 财政年份:
    2013
  • 资助金额:
    $ 40.98万
  • 项目类别:

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非洲人群中 HIV 氨基酸变异与 CHD1L 和 HLA I 类基因座的保护性宿主等位基因的关联
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