Reed D M, Torres J M, Brody J A
Am J Epidemiol. 1975 Apr;101(4):302-10. doi: 10.1093/oxfordjournals.aje.a112098.
The extraordinarily high rate of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD) in the Chamorro linguistic group on Guam suggested a genetic etiology for these diseases. Results of three studies are described. Two involved comparisons of the rates of disease in relatives and spouses of index patients and controls. In the third we examined offspring of doubly affected parents, 10 spouse pairs with ALS, 3 spouse pairs with PD and 13 spouse pairs in which 1 spouse had ALS and the other PD. Within the limitations of numbers and age of offspring, we found a tendency among siblings and offspring of ALS cases to have a higher risk than control relatives. Numbers were small and in no instance were significant differences encountered. Spouses of patients had at least as high risk of developing ALS or PD as any of the groups of blood relatives. A slightly higher age-specific rate of ALS and PD occurred in the offspring of doubly affected parents. The only group large enough for present analysis are 60 offspring of doubly affected ALS parents over the age of 20. Thus far only 3 have developed ALS. Within our entire patient population of 350 ALS cases and 219 PD cases there were 12 instances in which one parent of the patient was not Chamorro. In addition there is a consistent two- to threefold excess of affected males which could not be accounted for by competitive risks of death from other causes among females. While a familial tendency does exist these findings and observations are not compatible with any simple Mendelian form of inheritance. It is possible that genetic influences affect the occurrence of these diseases but our studies suggest that environmental factors play at least as important a role.
关岛查莫罗语族中肌萎缩侧索硬化症（ALS）和帕金森病痴呆症（PD）的发病率异常高，这表明这些疾病存在遗传病因。本文描述了三项研究的结果。其中两项研究比较了指数患者和对照者的亲属及配偶中的疾病发病率。在第三项研究中，我们检查了双亲均患病的后代、10对患ALS的配偶、3对患PD的配偶以及13对一方患ALS另一方患PD的配偶。在后代数量和年龄的限制范围内，我们发现ALS患者的兄弟姐妹和后代比对照亲属患这些疾病的风险更高。但数量较少，未发现任何显著差异。患者的配偶患ALS或PD的风险至少与任何一组血亲一样高。双亲均患病的后代中，ALS和PD的年龄特异性发病率略高。目前唯一足够大以供分析的群体是60名年龄超过20岁的双亲均患ALS的后代。到目前为止，只有3人患了ALS。在我们总共350例ALS患者和219例PD患者的人群中，有12例患者的一方父母不是查莫罗人。此外，患病男性始终比女性多两到三倍，这无法用女性因其他原因导致的竞争性死亡风险来解释。虽然确实存在家族倾向，但这些发现和观察结果与任何简单的孟德尔遗传形式都不相符。遗传因素可能会影响这些疾病的发生，但我们的研究表明环境因素至少起着同样重要的作用。
