title: Genome-wide association study identifies variants inHORMAD2associated with tonsillectomy.
abstract: Inflammation of the tonsils is a normal response to infection, but some individuals experience recurrent, severe tonsillitis and massive hypertrophy of the tonsils in which case surgical removal of the tonsils may be considered.
  
  
  
  To identify common genetic variants associated with tonsillectomy.
  
  
  
  We used tonsillectomy information from Danish health registers and carried out a genome-wide association study comprising 1464 patients and 12 019 controls of Northwestern European ancestry, with replication in an independent sample set of 1575 patients and 1367 controls.
  
  
  
  The variant rs2412971, intronic inHORMAD2at chromosome 22q12.2, was robustly associated with tonsillectomy (OR=1.22; p=1.48×10-9) and is highly correlated with SNPs previously found to be associated with IgA nephropathy, Crohn's disease (CD) and early onset inflammatory bowel disease (IBD). The risk allele for tonsillectomy corresponded to increased risk of IgA nephropathy and decreased risk of CD and IBD. We further performed lookup analyses of the top SNP for outcomes related to tonsillectomy in the combined discovery and replication sample and found that rs2412971 was associated with acute tonsillitis (OR=1.19; p=7.82×10-4), chronic disease of the tonsils (OR=1.19; p=2.32×10-6) and appendectomy (OR=1.18; p=1.13×10-3).
  
  
  
  We identified and replicated a genetic association at 22q12.2 with tonsillectomy. Further functional investigation is required to illuminate whether the molecular mechanisms underlying the genetic association involve general lymphoid hyper-reaction throughout the mucosa-associated lymphoid tissue system.
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Bjarke
authors.identifier: 0000-0003-1478-649X
authors.initials: B
authors.lastname: Feenstra
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Bager
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Xueping
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.|Department of Haematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Hjalgrim
authors.affiliation: Research Unit of Gynaecology & Obstetrics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Nohr
authors.affiliation: Danish Centre for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: David M
authors.initials: DM
authors.lastname: Hougaard
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Frank
authors.initials: F
authors.lastname: Geller
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.|Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.|Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Mads
authors.initials: M
authors.lastname: Melbye
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics*; D002877:Chromosomes, Human / Q000235:genetics; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results; D014068:Tonsillectomy
chemical_list: D018797:Cell Cycle Proteins
keywords: Genome-wide association study; IgA nephropathy; Inflammatory bowel disease; Mucosa-associated lymphoid tissue; Tonsillectomy