A genetic basis for infectious mononucleosis: evidence from a family study of hospitalized cases in Denmark

Clin Infect Dis. 2014 Jun;58(12):1684-9. doi: 10.1093/cid/ciu204. Epub 2014 Apr 2.

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: children; cohort; contagion; family study; genetics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Denmark / epidemiology
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics*
  • Hospitalization
  • Humans
  • Incidence
  • Infant
  • Infant, Newborn
  • Infectious Mononucleosis / epidemiology
  • Infectious Mononucleosis / genetics*
  • Male
  • Parents
  • Pedigree*
  • Risk Assessment
  • Siblings
  • Time Factors
  • Young Adult