Sadovnick A Dessa, Yee Irene M, Guimond Colleen, Reis Jacques, Dyment David A, Ebers George C
Department of Medical Genetics, Vancouver Coastal Health Authority-University of British Columbia Hospital, G-920 Detwiller Pavilion, Vancouver, British Columbia, Canada.
Am J Epidemiol. 2009 Aug 1;170(3):289-96. doi: 10.1093/aje/kwp143. Epub 2009 Jun 22.
The ages of onset in multiple sclerosis cases span more than 7 decades. Data are presented for affected relative pairs from a Canadian population base of 30,000 multiple sclerosis index cases (1993-2008). The effects of genetic sharing, parent of origin, intergenerational versus collinear differences, and gender on the ages of onset were evaluated in the following concordant pairs: monozygotic twins (n = 29), dizygotic twins (n = 10), siblings (n = 614), first cousins (n = 405), half siblings (n = 29), parent/child (n = 285), and aunt/uncle/niece/nephew (avunculars) (n = 289). Fisher's z test assessed intraclass correlation (r) for ages of onset. Correlations for monozygotic twins, dizygotic twins, full siblings, and first cousins were 0.60, 0.54, 0.20, and 0.10, respectively. Dizygotic twins resembled monozygotic twins more than siblings. The age-of-onset correlation for maternal half siblings (r = 0.37) was higher than that for paternal half siblings (r = 0.26), consistent with other observations suggesting an intrauterine environmental effect on multiple sclerosis risk. Intergenerational comparisons are complicated by substantial increases of multiple sclerosis incidence over time. Genetic loading (familial vs. sporadic cases) did not generally influence the age of onset, but correlation of age of onset in multiple sclerosis relative pairs was proportional to genetic sharing. A maternal parent-of-origin effect on the age of onset in collinear generations was suggested.
多发性硬化症病例的发病年龄跨度超过7个十年。数据来自加拿大一个由30000例多发性硬化症索引病例组成的人群（1993 - 2008年）中的患病亲属对。在以下同病对中评估了基因共享、亲代来源、代际与共线性差异以及性别对发病年龄的影响：同卵双胞胎（n = 29）、异卵双胞胎（n = 10）、兄弟姐妹（n = 614）、一级表亲（n = 405）、同父异母或同母异父的兄弟姐妹（n = 29）、父母/子女（n = 285）以及叔伯姑姨/侄甥（隔代亲属）（n = 289）。采用费舍尔z检验评估发病年龄的组内相关性（r）。同卵双胞胎、异卵双胞胎、亲兄弟姐妹和一级表亲的相关性分别为0.60、0.54、0.20和0.10。异卵双胞胎比亲兄弟姐妹更类似于同卵双胞胎。母系同父异母或同母异父的兄弟姐妹的发病年龄相关性（r = 0.37）高于父系同父异母或同母异父的兄弟姐妹（r = 0.26），这与其他表明子宫内环境对多发性硬化症风险有影响的观察结果一致。随着时间的推移，多发性硬化症发病率大幅上升，使得代际比较变得复杂。基因负荷（家族性病例与散发性病例）一般不影响发病年龄，但多发性硬化症亲属对中发病年龄的相关性与基因共享成正比。提示了母系亲代来源对共线性世代发病年龄的影响。
