Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Clin Infect Dis. 2014 Jun;58(12):1684-9. doi: 10.1093/cid/ciu204. Epub 2014 Apr 2.
Circumstantial evidence from genome-wide association and family studies of various Epstein-Barr virus-associated diseases suggests a substantial genetic component in infectious mononucleosis (IM) etiology. However, familial aggregation of IM has scarcely been studied.
We used data from the Danish Civil Registration System and the Danish National Hospital Discharge Register to study rate ratios of IM in a cohort of 2 823 583 Danish children born between 1971 and 2011. Specifically, we investigated the risk of IM in twins and in first-, second-, and third-degree relatives of patients with IM. In the analyses, IM was defined as a diagnosis of IM in a hospital contact. Effects of contagion between family members were dealt with by excluding follow-up time the first year after the occurrence of IM in a relative.
A total of 16 870 cases of IM were observed during 40.4 million person-years of follow-up from 1977 to 2011. The rate ratios and the associated 95% confidence intervals were 9.3 (3.0-29) in same-sex twins, 3.0 (2.6-3.5) in siblings, 1.9 (1.6-2.2) in children, 1.4 (1.3-1.6) in second-degree relatives, and 1.0 (0.9-1.2) in third-degree relatives of IM patients. The rate ratios were very similar for IM in children (aged 0-6 years) and older children/adolescents (aged 7-19 years).
We found evidence of familial aggregation of IM that warrants genome-wide association studies on IM disease etiology, especially to examine commonalities with causal pathways in other Epstein-Barr virus-related diseases.
全基因组关联研究和各种与 EBV 相关疾病的家族研究提供的间接证据表明,传染性单核细胞增多症(IM)的病因具有重要的遗传成分。然而,IM 的家族聚集性很少被研究。
我们使用丹麦民事登记系统和丹麦国家住院登记处的数据,对 1971 年至 2011 年间出生的 2823583 名丹麦儿童队列进行了 IM 发病率比值的研究。具体来说,我们调查了双胞胎以及 IM 患者的一级、二级和三级亲属中 IM 的风险。在分析中,IM 被定义为在医院就诊时诊断为 IM。通过排除在亲属发生 IM 的第一年的随访时间来处理家庭成员之间传染的影响。
在 1977 年至 2011 年期间,4040 万人年的随访中观察到 16870 例 IM 病例。同性别双胞胎的发病率比值及其 95%置信区间为 9.3(3.0-29),兄弟姐妹为 3.0(2.6-3.5),儿童为 1.9(1.6-2.2),二级亲属为 1.4(1.3-1.6),三级亲属为 1.0(0.9-1.2)。在儿童(0-6 岁)和较大儿童/青少年(7-19 岁)中,IM 的发病率比值非常相似。
我们发现了 IM 的家族聚集的证据,这需要对 IM 的疾病病因进行全基因组关联研究,特别是要检查与其他 EBV 相关疾病的因果途径的共性。