Applying the Bradford Hill criteria in the 21st century: how data integration has changed causal inference in molecular epidemiology.
Applying the Bradford Hill criteria in the 21st century: how data integration has changed causal inference in molecular epidemiology.
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DOI：
10.1186/s12982-015-0037-4
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发表时间：
2015
影响因子：
2.3
通讯作者：
Gross S
中科院分区：
文献类型：
--
作者：
Fedak KM;Bernal A;Capshaw ZA;Gross S
1965年，奥斯汀·布拉德福德·希尔爵士（Sir Austin Bradford Hill）发表了九个“观点”，以帮助确定观察到的流行病学关联是否是因果关系。从那时起，“布拉德福德希尔标准”已成为流行病学研究中最常引用的因果推理框架。然而，当希尔发表他的因果指南时--距离DNA双螺旋模型首次提出仅12年，距离人类基因组计划开始仅25年--人们对疾病因果关系的理解比今天更初级。遗传学、分子生物学、毒理学、暴露科学和统计学的进步提高了我们探索潜在因果关系的分析能力，并使我们更好地了解人类疾病发病和进展背后的复杂性。这些额外的因果推断工具需要重新评估在考虑经典流行病学研究之外的各种数据类型时，应如何解释每个Bradford Hill标准。在这里，我们探讨的标准的解释和应用的数据集成的影响。使用最近发现的人类疾病中的免疫应答关联的例子，我们讨论了新的方法，研究人员可以应用和解释布拉德福德山标准时，考虑使用现代分子技术，如表观遗传学，生物标志物，机制毒理学和遗传毒理学收集的数据。
In 1965, Sir Austin Bradford Hill published nine “viewpoints” to help determine if observed epidemiologic associations are causal. Since then, the “Bradford Hill Criteria” have become the most frequently cited framework for causal inference in epidemiologic studies. However, when Hill published his causal guidelines—just 12 years after the double-helix model for DNA was first suggested and 25 years before the Human Genome Project began—disease causation was understood on a more elementary level than it is today. Advancements in genetics, molecular biology, toxicology, exposure science, and statistics have increased our analytical capabilities for exploring potential cause-and-effect relationships, and have resulted in a greater understanding of the complexity behind human disease onset and progression. These additional tools for causal inference necessitate a re-evaluation of how each Bradford Hill criterion should be interpreted when considering a variety of data types beyond classic epidemiology studies. Herein, we explore the implications of data integration on the interpretation and application of the criteria. Using examples of recently discovered exposure–response associations in human disease, we discuss novel ways by which researchers can apply and interpret the Bradford Hill criteria when considering data gathered using modern molecular techniques, such as epigenetics, biomarkers, mechanistic toxicology, and genotoxicology.