German Cancer Research Center, Heidelberg, Germany.
Am J Gastroenterol. 2010 Jan;105(1):139-47. doi: 10.1038/ajg.2009.496. Epub 2009 Aug 25.
Familial risk estimates are useful for genetic counseling, etiological understanding, and design of gene identification studies. We wanted to estimate the associations of ulcerative colitis (UC) and Crohn's disease (CD) with 32 autoimmune and related diseases among parents and offspring, singleton siblings, twins, and spouses.
The Multigeneration Register in Sweden provides reliable access to information on families among 11.5 million individuals throughout the last century. The diseases in individual family members were obtained through linkage to the Hospital Discharge Register. Standardized incidence ratios (SIRs) and 95% confidence intervals were calculated as relative risks for UC/CD in family members of patients diagnosed with any of the 34 diseases compared with those lacking affected family members through years 1964-2004.
Among a total of 441,642 patients diagnosed with autoimmune and related conditions, 25,846 were diagnosed with UC and 18,885 with CD. Familial cases amounted to 5.4% of all UC patients and 6.5% of CD patients. SIR for UC was 3.9 (95% confidence interval 3.5-4.3) in offspring of affected parents, 4.6 (3.0-7.4) in siblings, 10.4 (6.5-15.8) in families of affected parents and siblings, and 6.3 (1.9-17.7) for monozygotic twins. The respective SIRs for CD were 6.0 (5.4-6.7), 6.3 (4.1-9.8), 34.0 (24.9-45.3), and 23.4 (10.1-51.1). All discordant associations, i.e., those between CD and other diseases, were also found for UC, including ankylosing spondylitis, asthma, polymyalgia rheumatica, psoriasis, and sarcoidosis. For UC, six additional associations were observed. No correlations between specific diseases were found among spouses, but between UC or CD and any disease it was 1.1 (1.0-1.1).
The concordant familial risks for UC and CD were lower than those commonly cited. Both diseases are associated with several autoimmune and related diseases, suggesting genetic sharing.
家族风险估计对于遗传咨询、病因理解和基因识别研究的设计都很有用。我们想要估计溃疡性结肠炎(UC)和克罗恩病(CD)与父母和子女、单卵双胞胎、双胞胎以及配偶中 32 种自身免疫性疾病和相关疾病之间的关联。
瑞典的多代登记处为获取上个世纪 1150 万人的家庭信息提供了可靠的途径。通过与住院记录登记处的链接,获取家族成员中个体疾病的信息。1964-2004 年间,将患者中任何 34 种疾病的家庭成员的标准发病率比(SIR)和 95%置信区间与缺乏受影响家庭成员的患者进行比较,计算 UC/CD 的相对风险。
在总共 441642 例被诊断为自身免疫性疾病和相关疾病的患者中,有 25846 例被诊断为 UC,18885 例被诊断为 CD。家族病例占所有 UC 患者的 5.4%,占 CD 患者的 6.5%。受影响父母的子女中 UC 的 SIR 为 3.9(95%置信区间 3.5-4.3),兄弟姐妹中为 4.6(3.0-7.4),受影响父母和兄弟姐妹的家庭中为 10.4(6.5-15.8),同卵双胞胎中为 6.3(1.9-17.7)。相应的 CD 的 SIR 为 6.0(5.4-6.7)、6.3(4.1-9.8)、34.0(24.9-45.3)和 23.4(10.1-51.1)。所有不一致的关联,即 CD 与其他疾病之间的关联,也见于 UC,包括强直性脊柱炎、哮喘、巨细胞性多关节炎、银屑病和结节病。UC 还观察到另外六个关联。配偶之间未发现特定疾病之间的相关性,但 UC 或 CD 与任何疾病之间的相关性为 1.1(1.0-1.1)。
UC 和 CD 的一致性家族风险低于通常引用的风险。这两种疾病都与多种自身免疫性疾病和相关疾病有关,提示存在遗传共享。