Sadovnick A D, Yee I M, Ebers G C, Risch N J
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Neurology. 1998 Mar;50(3):719-23. doi: 10.1212/wnl.50.3.719.
MS is believed to be a complex trait determined by genetic and nongenetic factors. Data suggest that MS susceptibility and age at onset are each, at least to some extent, under genetic control. The present study carefully examined five covariates (sex of the index case, sex of the sibling, birth cohort of the sibling [< or = 1919, 1920 to 1939, > or = 1940], age of MS onset in the index patient (< or = 20 years, 21 to 30 years, 31 to 40 years, > 40 years), and MS disease status of the parents [i.e., MS present in one parent or no parent with MS]) that may influence the familial risk of MS in a large cohort of 1,896 MS patients and 8,878 of their first-degree relatives. Of these, sex of the sibling, parental MS status, and index patient onset age were the important factors influencing MS risks to siblings. The results of this study are (1) the index-patient-onset-age effect suggests that individuals with a greater genetic loading (i.e., a greater contribution of susceptibility alleles) have an earlier age at onset and (2) genetic loading is substantially increased in individuals with an affected parent. These data are important both for genetic counseling and gene identification studies.
多发性硬化症（MS）被认为是一种由遗传和非遗传因素决定的复杂性状。数据表明，MS易感性和发病年龄至少在一定程度上受遗传控制。本研究仔细检查了五个协变量（索引病例的性别、同胞的性别、同胞的出生队列[≤1919年、1920年至1939年、≥1940年]、索引患者的MS发病年龄[≤20岁、21至30岁、31至40岁、>40岁]以及父母的MS疾病状态[即一方父母患有MS或父母均无MS]），这些协变量可能会影响1896例MS患者及其8878名一级亲属这一大型队列中MS的家族风险。其中，同胞的性别、父母的MS状态和索引患者的发病年龄是影响同胞患MS风险的重要因素。本研究的结果为：（1）索引患者发病年龄效应表明，遗传负荷较大（即易感等位基因贡献较大）的个体发病年龄较早；（2）有患病父母的个体遗传负荷显著增加。这些数据对于遗传咨询和基因鉴定研究都很重要。
