Hemminki Kari, Shu Xiaochen, Li Xinjun, Ji Jianguang, Sundquist Kristina, Sundquist Jan
Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany.
Eur J Endocrinol. 2009 Oct;161(4):623-9. doi: 10.1530/EJE-09-0349. Epub 2009 Aug 6.
Familial clustering of a disease is an indicator of a possible heritable cause, provided that environmental sharing can be excluded. Thus, data on familial risks are important for genetic studies and for clinical genetic counseling.
We carried out a nationwide family study on nontoxic and toxic nodular goiters, and Graves' disease in order to search for familial clustering of these diseases at the population level.
The Swedish Multigeneration Register on 0-75 year old subjects was linked to the Hospital Discharge Register from years 1987 to 2007. Standardized incidence ratios (SIRs) were calculated for offspring of affected parents and for siblings by comparing to those whose relatives had no hospitalization for thyroid disease.
The number of hospitalized patients in the offspring generations was 11 659 for nontoxic goiter, 9514 for Graves' disease, and 1728 for toxic nodular goiter. Familial cases accounted for 8.2, 5.2, and 2.1% of all patients respectively. The highest familial risk for offspring of affected parents was noted for Graves' disease (SIR 3.87), followed by toxic nodular goiter (3.37) and nontoxic goiter (3.15). Familial risks were higher for affected siblings: toxic nodular goiter (11.66), Graves' disease (5.51), and nontoxic goiter (5.40). Weaker familial associations were observed between the three diseases.
To our knowledge this is a first population-based family study on these thyroid diseases. The observed high familial aggregation for defined thyroid diseases cannot be explained by the known genetic basis, calling for further studies into genetic and environmental etiology of thyroid diseases.
疾病的家族聚集性是可能存在遗传病因的一个指标，前提是可以排除环境因素的共同影响。因此，家族风险数据对于基因研究和临床遗传咨询非常重要。
我们开展了一项关于非毒性和毒性结节性甲状腺肿以及格雷夫斯病的全国性家庭研究，以探寻这些疾病在人群层面的家族聚集性。
将瑞典0至75岁人群的多代登记册与1987年至2007年的医院出院登记册相链接。通过与亲属未因甲状腺疾病住院的人群进行比较，计算出患病父母的后代以及兄弟姐妹的标准化发病率（SIR）。
后代中因非毒性甲状腺肿住院的患者有11659例，因格雷夫斯病住院的有9514例，因毒性结节性甲状腺肿住院的有1728例。家族性病例分别占所有患者的8.2%、5.2%和2.1%。患病父母的后代中，格雷夫斯病的家族风险最高（SIR为3.87），其次是毒性结节性甲状腺肿（3.37）和非毒性甲状腺肿（3.15）。患病兄弟姐妹的家族风险更高：毒性结节性甲状腺肿（11.66）、格雷夫斯病（5.51）和非毒性甲状腺肿（5.40）。在这三种疾病之间观察到较弱的家族关联。
据我们所知，这是首次基于人群的关于这些甲状腺疾病的家庭研究。所观察到的特定甲状腺疾病的高家族聚集性无法用已知的遗传基础来解释，这需要对甲状腺疾病的遗传和环境病因进行进一步研究。
