TRANSDISCIPLINARY RESEARCH ON GENETICS OF COMPLEX TRAITS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。描述（由申请人提供）：每年有数十亿张处方被开出，希望能改善数百万美国人的健康状况，预防疾病。不幸的是，这些药物并不像希望的那样在每个人身上起作用，其他人则遭受副作用，导致大量的发病率和死亡率。尽管几十年来人们已经知道药物反应的遗传变异性在限制药物的疗效和安全性方面发挥着关键作用，但遗传学、生物信息学、药理学、流行病学和生物统计学的最新进展为理解遗传变异性如何改变药物反应铺平了道路。尽管有这样的前景，基因-药物相互作用的性质是复杂的，该领域的进展一直受到缺乏真正的跨学科方法的阻碍。只有通过遗传学、生物信息学、药理学、流行病学、生物统计学和生物伦理学等学科在一个新的跨学科领域（我们称之为人类药物基因组流行病学（HPE））中的协调和持续合作，才能完全理解对药物的可变反应的遗传基础，并在人群中适当应用这些信息。HPE不仅仅是多个学科的合并，并行或按顺序工作，而是一种新的研究范式，必须开发协同工作的新方法，以解决跨学科研究的科学，后勤和智力障碍。在本申请中，来自这些学科的一组经验丰富的研究人员，在丰富和支持性的学术环境中工作，提出建立跨学科合作，其目的是通过制定针对跨学科研究的所有三个障碍的战略，开发独特和可持续的方法来解决可变药物反应的重大和复杂的生物医学问题：1）科学：通过开发研究设计和统计方法，旨在解决遗传对药物反应的复杂、高维性质的问题，2）Logistics：通过开发新策略，提高HPE研究的协调性和效率，以及3）智力：通过设计创新和可持续的方法，提高各学科对彼此科学背景、所提供机会以及独特方法和语言的认识。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. DESCRIPTION (provided by applicant): Billions of prescriptions are written each year in the hopes of improving health and preventing disease in millions of Americans. Unfortunately, these medications do not work as hoped in everyone, and others suffer from side effects, leading to substantial morbidity and mortality. Although genetic variability in the response to medications has been known for decades to play a critical role in limiting the efficacy and safety of drugs, recent advances in genetics, bioinformatics, pharmacology, epidemiology, and biostatistics have paved the way for tremendous gains in understanding how genetic variability can alter drug response. Despite this promise, the nature of gene-drug interactions is complex, and progress in the field has been hampered by the lack of a true interdisciplinary approach. A complete understanding of the genetic basis for variable responses to medications and appropriate application of this information in human populations will come only through a coordinated and sustained collaboration among the disciplines of genetics, bioinformatics, pharmacology, epidemiology, biostatistics, and bioethics in a new interdisciplinary field that we call Human Pharmacogenomic Epidemiology (HPE). HPE is not simply the merger of multiple disciplines, working in parallel or sequence, but rather a new paradigm of research that must develop novel ways of working synergistically to address the scientific, logistical, and intellectual barriers to interdisciplinary research. In this application, a group of experienced investigators from each of these disciplines, working within an enriched and supportive academic environment, proposes to develop an interdisciplinary collaboration whose aims are to develop unique and sustainable approaches to solving the significant and complex biomedical problem of variable drug response by developing strategies targeted at all three barriers to interdisciplinary research: 1) Scientific: by developing study design and statistical methods aimed at solving problems of the complex, high-dimensional nature of genetic influences on response to medications, 2) Logistical: by developing new strategies that improve the coordination and efficiency of HPE research, and 3) Intellectual: by designing innovative and sustainable approaches to improve the appreciation among the disciplines of each others' scientific context, opportunities offered, and distinct methods and languages.