Sawcer Stephen
University of Cambridge, Department of Clinical Neurosciences, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK.
Ann Indian Acad Neurol. 2009 Oct;12(4):206-14. doi: 10.4103/0972-2327.58272.
marked geographical variation in prevalence and substantial familial clustering. At first sight, geographic variation would seem to imply an environmental cause for the disease, while familial clustering would seem to suggest that genetic factors have the predominant etiological effect. However, given that geographic variation in prevalence could result from variation in the frequency of genetic risk alleles and that familial clustering might result from shared environmental exposure rather than shared genetic risk alleles, it is clear that these crude inferences are unreliable. Epidemiologists have been resourceful in their attempts to resolve this apparent conflict between "nurture and nature" and have employed a whole variety of sophisticated methods to try and untangle the etiology of multiple sclerosis. The body of evidence that has emerged from these efforts has formed the foundation for decades of research seeking to identify relevant genes and this is the obvious place to start any consideration of the genetics of multiple sclerosis.
多发性硬化症的流行病学已得到广泛研究,且始终呈现出两个特征:患病率存在显著的地理差异以及明显的家族聚集性。乍一看,地理差异似乎意味着该疾病由环境因素导致,而家族聚集性则似乎表明遗传因素具有主要的病因学作用。然而,鉴于患病率的地理差异可能源于遗传风险等位基因频率的变化,且家族聚集性可能是由于共同的环境暴露而非共同的遗传风险等位基因所致,显然这些粗略的推断并不可靠。流行病学家在试图解决“先天与后天”之间这一明显冲突时足智多谋,他们采用了各种各样复杂的方法来尝试理清多发性硬化症的病因。这些努力所产生的证据体系为数十年来旨在识别相关基因的研究奠定了基础,而这也是开始任何关于多发性硬化症遗传学研究的明显起点。