Newman T B, Browner W S
Department of Epidemiology and International Health, University of California, San Francisco 94143.
Teratology. 1988 Oct;38(4):303-11. doi: 10.1002/tera.1420380402.
The epidemiologic approach to determining the etiology of disease involves identification of potential risk factors and then comparison of disease incidence among people with varying levels of exposure to the potential risk factors. This paper defines risk factors which correspond to different levels of genetic and environmental proximity to index cases of birth defects. Genetic proximity is estimated by the coefficient of relationship (R): 0.5 for siblings and dizygotic twins and 1.0 for monozygotic twins. Environmental proximity is measured by a combination of two variables: one variable for those potentially preventable risk factors common to siblings (S) and another for those common only to twins (T). Discordance in identical twins is attributed to a third type of environmental factors (U) that are unshared by twins and include random (stochastic) factors. The association between these risk factors and birth defects is estimated by using a linear model of the correlation of liability for different relatives. The coefficients derived from the model reflect the relative importance of genetic and different types of environmental risk factors as causes for the defects and can be used to identify birth defects most likely to be caused by measurable and possibly preventable risk factors. These defects could then be assigned high priority for future studies and preventive efforts.
确定疾病病因的流行病学方法包括识别潜在风险因素，然后比较接触不同水平潜在风险因素人群的疾病发病率。本文定义了与出生缺陷指数病例在遗传和环境方面不同程度接近对应的风险因素。遗传接近程度通过亲缘系数（R）来估计：兄弟姐妹和异卵双胞胎为0.5，同卵双胞胎为1.0。环境接近程度通过两个变量的组合来衡量：一个变量用于兄弟姐妹共有的那些潜在可预防风险因素（S），另一个变量用于仅双胞胎共有的那些因素（T）。同卵双胞胎之间的不一致归因于双胞胎不共有的第三种环境因素（U），包括随机（随机）因素。通过使用不同亲属易感性相关性的线性模型来估计这些风险因素与出生缺陷之间的关联。从该模型得出的系数反映了遗传和不同类型环境风险因素作为缺陷病因的相对重要性，可用于识别最有可能由可测量且可能可预防的风险因素引起的出生缺陷。然后可以将这些缺陷列为未来研究和预防工作的高度优先事项。
