Peter Bager, Giulia Corn, Jan Wohlfahrt, Heather A Boyd, Bjarke Feenstra, Mads Melbye

The tonsils are immunological gatekeepers against pathogens. Immunological response to tonsillitis may vary clinically from no enlargement of the tonsils to nearly obstructive conditions. In this investigation, we studied the familial aggregation of tonsillectomy, as an indicator of the extent to which tonsillar immune responses to infections might be genetically controlled. Data on kinship relations and vital status from the Danish Civil Registration System were used to establish a cohort of Danes with relatives born since 1977. Tonsillectomies in all hospitals and clinics from 1977 to 2013 were identified in national registers together with the indication for tonsillectomy. Rate ratios (RRs) for tonsillectomy >1 year after tonsillectomy in specific types of relatives (first to fourth degree) were estimated in Poisson regression models with adjustment for calendar period, sex, age, and total number of specified relatives. A cohort of 2.4 million persons was followed for 44,100,697 million person-years (mean 18.4 years/person), and included 148,190 tonsillectomies. RRs of tonsillectomy were consistently higher when the relatedness and the number of tonsillectomized relatives were higher. RRs were similar in boys and girls, but were larger in early childhood. Additional analyses suggested that this relatively higher RR at younger ages was due to a larger influence of shared environment at younger ages, whereas the genetic influence was similar at all ages. Results were similar for tonsillectomies performed strictly due to tonsillitis. Genetic factors appear to predispose to severe tonsillitis underlying tonsillectomies, regardless of age and sex. Further studies are needed to understand how genes regulate the tonsils' immune response against infections.