Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Department of Medicine, Karlstad Central Hospital, Karlstad, Sweden.
Eur J Endocrinol. 2020 May;182(5):473-480. doi: 10.1530/EJE-20-0049.
Co-aggregation of autoimmune diseases is common, suggesting partly shared etiologies. Genetic factors are believed to be important, but objective measures of environmental vs heritable influences on co-aggregation are absent. With a novel approach to twin studies, we aimed at estimating heritability and genetic overlap in seven organ-specific autoimmune diseases.
Prospective twin cohort study.
We used a cohort of 110 814 twins to examine co-aggregation and heritability of Hashimoto's thyroiditis, atrophic gastritis, celiac disease, Graves' disease, type 1 diabetes, vitiligo and Addison's disease. Hazard ratios (HR) were calculated for twins developing the same or different disease as compared to their co-twin. The differences between monozygotic and dizygotic twin pairs were used to estimate the genetic influence on co-aggregation. Heritability for individual disorders was calculated using structural equational modeling adjusting for censoring and truncation of data.
Co-aggregation was more pronounced in monozygotic twins (median HR: 3.2, range: 2.2-9.2) than in dizygotic twins (median HR: 2.4, range: 1.1-10.0). Heritability was moderate for atrophic gastritis (0.38, 95% CI: 0.23-0.53) but high for all other diseases, ranging from 0.60 (95% CI: 0.49-0.71) for Graves' disease to 0.97 (95% CI: 0.91-1.00) for Addison's disease.
Overall, co-aggregation was more pronounced in monozygotic than in dizygotic twins, suggesting that disease overlap is largely attributable to genetic factors. Co-aggregation was common, and twins faced up to a ten-fold risk of developing diseases not present in their co-twin. Our results validate and refine previous heritability estimates based on smaller twin cohorts.
自身免疫性疾病的共同发病较为常见，提示其部分病因相同。遗传因素被认为很重要，但目前尚缺乏针对环境因素与遗传因素对共同发病影响的客观衡量指标。本研究采用一种新的双胞胎研究方法，旨在评估七种器官特异性自身免疫性疾病的遗传易感性和遗传重叠程度。
前瞻性双胞胎队列研究。
我们利用 110814 对双胞胎的队列资料，研究桥本甲状腺炎、萎缩性胃炎、乳糜泻、格雷夫斯病、1 型糖尿病、白癜风和艾迪生病的共同发病情况及其遗传易感性。与同卵双胞胎相比，计算双胞胎发生相同或不同疾病的风险比（HR）。比较单卵双生子和双卵双生子之间的差异，用于估计遗传因素对共同发病的影响。使用结构方程模型对个体疾病的遗传易感性进行计算，同时对数据的删失和截断进行调整。
同卵双胞胎（中位数 HR：3.2，范围：2.2-9.2）的共同发病比双卵双胞胎（中位数 HR：2.4，范围：1.1-10.0）更明显。萎缩性胃炎的遗传度中等（0.38，95%CI：0.23-0.53），而其他所有疾病的遗传度均较高，从格雷夫斯病的 0.60（95%CI：0.49-0.71）到艾迪生病的 0.97（95%CI：0.91-1.00）。
总体而言，同卵双胞胎的共同发病比双卵双胞胎更明显，提示疾病重叠主要归因于遗传因素。共同发病较为常见，双胞胎自身患未在同卵双胞胎中出现的疾病的风险高达十倍。本研究结果验证并细化了之前基于较小双胞胎队列的遗传度估计。
