评估遗传祖先与临床现象之间的关系
Jacqueline A Piekos1, Jeewoo Kim, Jacob M Keaton
1Vanderbilt Genetics Institute, Vanderbilt University, Nashville, Tennessee 37203, United States2Department of Obstetrics and Gynecology, Vanderbilt University Medical Center Nashville, Tennessee 37232, United States3Department of Biomedical Informatics, Vanderbilt University Medical Center Nashville, Tennessee 37232, United States^Work partially supported by T32GM080178.
Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing
|December 31, 2023
概括
这项研究超越了种族,使用遗传祖先比例来分析健康状况. 研究结果揭示了祖先与高血压等疾病之间的非线性关系,这表明先进的建模可以获得更好的临床见解.
科学领域:
- 基因组学就是基因组学.
- 人口遗传学 人口遗传学
- 临床信息学 临床信息学
背景情况:
- 种族是一种社会构造,而不是精确的生物学决定因素.
- 地理祖先为遗传变异提供了更准确的代理.
- 了解祖先-表型联系对于个性化医学至关重要.
研究的目的:
- 调查遗传祖先比例与临床表型之间的关联.
- 确定线性或非线性模型是否最好地描述这些关系.
- 推动研究超越种族,以更细致的理解对健康的遗传影响.
主要方法:
- 使用了范德比尔特大学医学中心的BioVU生物银行.
- 使用1000个基因组参考计算了六个遗传祖先比例 (EAFR,WAFR,NEUR,SEUR,EAS,SAS).
- 采用了全现象协会研究 (PheWAS),后勤回归和受限立方线 (RCS) 建模.
主要成果:
- PheWAS发现了EAFR,WAFR和SEUR的显著瘤丰富,以及SEUR,NEUR,SAS和EAS的妊娠并发症.
- 高血压和心房显示与EAFR,WAFR和SEUR的线性关系,但与NEUR的非线性 (RCS) 关系.
- 功能衰竭与SAS祖先呈现线性关系,与EAS祖先呈现非线性关系 (RCS).
结论:
- 遗传祖先比例与各种临床表型有显著的关联.
- 像RCS这样的非线性建模技术对于准确捕捉一些祖先-表型关系至关重要.
- 这项研究支持在临床研究中从基于种族的分析转向基于祖先的分析.
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