Genome-wide association study identifies variants in HORMAD2 associated with tonsillectomy

Bjarke Feenstra, Peter Bager, Xueping Liu, Henrik Hjalgrim, Ellen A Nohr, David M Hougaard, Frank Geller, Mads Melbye

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

BACKGROUND: 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.

OBJECTIVE: To identify common genetic variants associated with tonsillectomy.

METHODS: 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.

RESULTS: The variant rs2412971, intronic in HORMAD2 at 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)).

CONCLUSIONS: 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.

OriginalsprogEngelsk
TidsskriftJournal of Medical Genetics
Vol/bind54
Udgave nummer5
Sider (fra-til)358-364
ISSN0022-2593
DOI
StatusUdgivet - maj 2017

Fingeraftryk

Genome-Wide Association Study
Inflammatory Bowel Diseases
Crohn Disease
Single Nucleotide Polymorphism
Lymphoid Tissue
Mucous Membrane
Alleles
Health

Citer dette

Feenstra, Bjarke ; Bager, Peter ; Liu, Xueping ; Hjalgrim, Henrik ; Nohr, Ellen A ; Hougaard, David M ; Geller, Frank ; Melbye, Mads. / Genome-wide association study identifies variants in HORMAD2 associated with tonsillectomy. I: Journal of Medical Genetics. 2017 ; Bind 54, Nr. 5. s. 358-364.
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title = "Genome-wide association study identifies variants in HORMAD2 associated with tonsillectomy",
abstract = "BACKGROUND: 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.OBJECTIVE: To identify common genetic variants associated with tonsillectomy.METHODS: 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.RESULTS: The variant rs2412971, intronic in HORMAD2 at 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)).CONCLUSIONS: 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.",
keywords = "Genome-wide association study, IgA nephropathy, Inflammatory bowel disease, Mucosa-associated lymphoid tissue, Tonsillectomy, Chromosomes, Human/genetics, Genome-Wide Association Study, Polymorphism, Single Nucleotide/genetics, Reproducibility of Results, Humans, Cell Cycle Proteins/genetics, Genetic Loci",
author = "Bjarke Feenstra and Peter Bager and Xueping Liu and Henrik Hjalgrim and Nohr, {Ellen A} and Hougaard, {David M} and Frank Geller and Mads Melbye",
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Feenstra, B, Bager, P, Liu, X, Hjalgrim, H, Nohr, EA, Hougaard, DM, Geller, F & Melbye, M 2017, 'Genome-wide association study identifies variants in HORMAD2 associated with tonsillectomy', Journal of Medical Genetics, bind 54, nr. 5, s. 358-364. https://doi.org/10.1136/jmedgenet-2016-104304

Genome-wide association study identifies variants in HORMAD2 associated with tonsillectomy. / Feenstra, Bjarke; Bager, Peter; Liu, Xueping; Hjalgrim, Henrik; Nohr, Ellen A; Hougaard, David M; Geller, Frank; Melbye, Mads.

I: Journal of Medical Genetics, Bind 54, Nr. 5, 05.2017, s. 358-364.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Genome-wide association study identifies variants in HORMAD2 associated with tonsillectomy

AU - Feenstra, Bjarke

AU - Bager, Peter

AU - Liu, Xueping

AU - Hjalgrim, Henrik

AU - Nohr, Ellen A

AU - Hougaard, David M

AU - Geller, Frank

AU - Melbye, Mads

N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

PY - 2017/5

Y1 - 2017/5

N2 - BACKGROUND: 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.OBJECTIVE: To identify common genetic variants associated with tonsillectomy.METHODS: 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.RESULTS: The variant rs2412971, intronic in HORMAD2 at 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)).CONCLUSIONS: 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.

AB - BACKGROUND: 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.OBJECTIVE: To identify common genetic variants associated with tonsillectomy.METHODS: 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.RESULTS: The variant rs2412971, intronic in HORMAD2 at 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)).CONCLUSIONS: 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.

KW - Genome-wide association study

KW - IgA nephropathy

KW - Inflammatory bowel disease

KW - Mucosa-associated lymphoid tissue

KW - Tonsillectomy

KW - Chromosomes, Human/genetics

KW - Genome-Wide Association Study

KW - Polymorphism, Single Nucleotide/genetics

KW - Reproducibility of Results

KW - Humans

KW - Cell Cycle Proteins/genetics

KW - Genetic Loci

U2 - 10.1136/jmedgenet-2016-104304

DO - 10.1136/jmedgenet-2016-104304

M3 - Journal article

C2 - 27941131

VL - 54

SP - 358

EP - 364

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

SN - 0022-2593

IS - 5

ER -