Khoury M J, Flanders W D
Birth Defects and Genetic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Epidemiology. 1995 Sep;6(5):511-9. doi: 10.1097/00001648-199509000-00009.
In many case-control studies of common diseases, investigators use family history information to assess familial aggregation of the disease and the influence of genetic factors. Positive family history among first-degree relatives is often used as a risk factor, and its odds ratio is calculated. Although the limitations of this approach have been discussed, it is not clear how much impact such limitations could have on measuring familial aggregation. To assess this impact, we compare odds ratios derived from using a positive family history in case-control studies with measures of relative risk derived from comparing lifetime risks of disease among first-degree relatives of case subjects with those among first-degree relatives of control subjects. Positive family history is a function of the number of relatives, the background risk of disease, the age distribution of relatives, and the correlation in risk among relatives. It can be shown that even without case-control differences in the number or ages of relatives, positive family history tends to overestimate relative risk measures applied to individual relatives. This overestimation is accentuated with increasing frequency of the disease, with increasing number of relatives, and for diseases with earlier age at onset. It is further affected by even small case-control differences in family size and age distribution of relatives. As such, positive family history is not a stable indicator of familial aggregation across different case-control studies of the same disease.
在许多常见疾病的病例对照研究中，研究人员利用家族史信息来评估疾病的家族聚集性以及遗传因素的影响。一级亲属中的阳性家族史常被用作一个风险因素，并计算其比值比。尽管这种方法的局限性已被讨论过，但尚不清楚这些局限性在测量家族聚集性方面会产生多大影响。为了评估这种影响，我们将病例对照研究中使用阳性家族史得出的比值比与通过比较病例组一级亲属与对照组一级亲属的疾病终生风险得出的相对风险测量值进行比较。阳性家族史是亲属数量、疾病背景风险、亲属年龄分布以及亲属间风险相关性的函数。可以证明，即使病例组和对照组在亲属数量或年龄上没有差异，阳性家族史也往往会高估应用于个体亲属的相对风险测量值。随着疾病发生频率的增加、亲属数量的增加以及发病年龄较早的疾病，这种高估会更加明显。它还会受到病例组和对照组在家庭规模和亲属年龄分布上即使很小的差异的进一步影响。因此，在同一疾病的不同病例对照研究中，阳性家族史并不是家族聚集性的一个稳定指标。
