Bulman D E, Sadovnick A D, Ebers G C
Multiple Sclerosis Clinic, University of Western Ontario, London, Canada.
Brain. 1991 Apr;114 ( Pt 2):937-50. doi: 10.1093/brain/114.2.937.
We have evaluated genetic and environmental influences in multiple sclerosis (MS) by comparing age of onset in 99 sibling pairs concordant for the disease. We used three methods of analysis: (1) comparison of mean differences in age of onset and year of onset, (2) linear regression of differences in age or year of onset vs difference in ages, and (3) intraclass correlation of age of onset which is also used for monozygotic twins concordant for MS. Comparison of the mean differences in age of onset or year of onset is found to be inappropriate and potentially misleading. No significant results were found in linear regression of the age of onset or year of onset vs differences in ages, although a trend towards onset at the same age is present. However, nontwin siblings show a significant intraclass correlation for age of onset (P less than 0.01) as is seen in genetic disorders. A stronger intraclass correlation in age of onset in concordant monozygotic twins vs concordant sibling pairs further suggests that age of onset is partly under genetic control, assuming common exposure to an environmental agent. The results give little support for common exposure to an environmental trigger in concordant MS sibling pairs. They are consistent with a mixture of random independent exposures and common exposures leading to the development of the disease, with the former predominating.
我们通过比较99对患多发性硬化症（MS）的同病兄弟姐妹对的发病年龄，评估了遗传和环境因素对多发性硬化症的影响。我们采用了三种分析方法：（1）比较发病年龄和发病年份的平均差异；（2）发病年龄或发病年份的差异与年龄差异的线性回归；（3）发病年龄的组内相关性，该方法也用于患MS的同卵双胞胎。结果发现，比较发病年龄或发病年份的平均差异是不合适的，而且可能会产生误导。在发病年龄或发病年份与年龄差异的线性回归中，未发现显著结果，尽管存在发病年龄相同的趋势。然而，非同卵双胞胎的发病年龄显示出显著的组内相关性（P小于0.01），这在遗传疾病中也可见。与同病兄弟姐妹对相比，同病同卵双胞胎的发病年龄组内相关性更强，这进一步表明，假设共同暴露于环境因素下，发病年龄部分受遗传控制。这些结果几乎不支持同病MS兄弟姐妹对共同暴露于环境触发因素的观点。它们与导致疾病发生的随机独立暴露和共同暴露的混合情况一致，其中前者占主导。
