Epidemiology, epigenetics and the 'Gloomy Prospect': embracing randomness in population health research and practice
Epidemiology, epigenetics and the 'Gloomy Prospect': embracing randomness in population health research and practice
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DOI：
10.1093/ije/dyr117
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发表时间：
2011-06-01
影响因子：
7.7
通讯作者：
Smith, George Davey
中科院分区：
文献类型：
--
作者：
Smith, George Davey
流行病学家的目标是查明可改变的疾病原因，这往往是将流行病学调查结果应用于公共卫生方案、卫生服务规划和临床医学的先决条件。尽管在确定病因方面取得了成功，但人们经常声称，即使是对肺癌和冠心病等合理理解的疾病，也缺少其他原因。有几条证据表明，从传记到亚细胞，很大程度上是偶然事件，对疾病风险有重要的随机因素，在个人层面上，这种因素在流行病学上是不可处理的。表观遗传的影响为这种看似随机的过程提供了一种时髦的当代解释。偶然事件--比如一个特定的终生吸烟者毫发无损地活到100岁--在群体水平上被平均了。因此，人口一级的差异（例如长期趋势或行政区域之间的差异）完全可以用似乎只占个人一级风险一小部分的因果因素来解释。在公共卫生方面，大多数疾病病例的可改变原因可能已经确定，但仍在继续进行徒劳的追逐，试图规范世界的随机性，特定的个人将屈服于这种随机性。对个性化医疗的追求是这一梦想的当代表现。关于生物体发展中存在随机性的原因，进化论早就有了明确的解释，即在不断变化的环境中提供生存优势。此外，在一个层次上近乎随机的东西在更高层次上几乎可以完全预测的基本概念是许多系统的一种涌现特性，从粒子物理学到社会科学。这些考虑表明，在我们进入表观基因组的十年之际，流行病学方法仍将富有成效。
Epidemiologists aim to identify modifiable causes of disease, this often being a prerequisite for the application of epidemiological findings in public health programmes, health service planning and clinical medicine. Despite successes in identifying causes, it is often claimed that there are missing additional causes for even reasonably well-understood conditions such as lung cancer and coronary heart disease. Several lines of evidence suggest that largely chance events, from the biographical down to the sub-cellular, contribute an important stochastic element to disease risk that is not epidemiologically tractable at the individual level. Epigenetic influences provide a fashionable contemporary explanation for such seemingly random processes. Chance events-such as a particular lifelong smoker living unharmed to 100 years-are averaged out at the group level. As a consequence population-level differences (for example, secular trends or differences between administrative areas) can be entirely explicable by causal factors that appear to account for only a small proportion of individual-level risk. In public health terms, a modifiable cause of the large majority of cases of a disease may have been identified, with a wild goose chase continuing in an attempt to discipline the random nature of the world with respect to which particular individuals will succumb. The quest for personalized medicine is a contemporary manifestation of this dream. An evolutionary explanation of why randomness exists in the development of organisms has long been articulated, in terms of offering a survival advantage in changing environments. Further, the basic notion that what is near-random at one level may be almost entirely predictable at a higher level is an emergent property of many systems, from particle physics to the social sciences. These considerations suggest that epidemiological approaches will remain fruitful as we enter the decade of the epigenome.