In the era of complex disease genetics, the consideration of familial risks is important in the assessment of the likely success of these studies. In the present article, we study familial risks for multiple sclerosis (MS) among parents and offspring, singleton siblings, twins, and spouses when a family member was diagnosed with MS or any of 33 other autoimmune diseases. The availability of a Multigeneration Register in Sweden provides a reliable access to families throughout the last century. The diseases in individual family members were obtained through linkage to the Hospital Discharge Register. With a total patient population of 425,102 of whom 11,154 were diagnosed with MS, this is the largest population-based family study on these diseases to date. Standardized incidence ratio (SIR) was calculated for family member of MS patients compared to those lacking an affected family member. SIR for MS was 5.94 (6.12 when parents were aged <73 years) in offspring of affected parents, 6.25 in singleton siblings, 9.09 in twins, and 1.50 (nonsignificant) in spouses; the SIRs did not depend on the gender. The SIRs for MS were 1.84 when a parent was diagnosed with amyotrophic lateral sclerosis and 1.14 with parental asthma. The overall risk of MS was 1.21 when a parent was diagnosed with any autoimmune disease. The genes, so far associated with MS, explain little of the familial aggregation of MS, calling for further efforts in gene identification. The shared familial risks of MS with amyotrophic lateral sclerosis and asthma suggest shared genetic basis.

译文

在复杂疾病遗传学时代,对家族风险的考虑对于评估这些研究的可能成功至关重要。在本文中,我们研究了家庭成员被诊断出患有MS或33种其他自身免疫性疾病时,父母和后代,单身兄弟姐妹,双胞胎和配偶中多发性硬化症 (MS) 的家族风险。上个世纪,瑞典拥有多世代登记册,为家庭提供了可靠的访问途径。个别家庭成员的疾病是通过与医院出院登记册的联系获得的。共有425,102名患者,其中11,154名被诊断出患有MS,这是迄今为止针对这些疾病的最大的基于人群的家庭研究。与缺少受影响的家庭成员相比,计算了MS患者的家庭成员的标准化发病率 (SIR)。MS的SIR在受影响父母的后代中5.94 (6.12在父母年龄 <73岁时),在单身兄弟姐妹中6.25,在双胞胎中9.09,在配偶中1.50 (不显着); SIRs不取决于性别。当父母被诊断患有肌萎缩性侧索硬化症并1.14父母哮喘时,MS的SIRs被1.84。当父母被诊断患有任何自身免疫性疾病时,MS的总体风险1.21。到目前为止,与MS相关的基因几乎无法解释MS的家族聚集,因此需要进一步的基因鉴定努力。肌萎缩性侧索硬化症和哮喘的MS共同家族风险表明有共同的遗传基础。

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