Genome-wide association study for acute otitis media in children identifies FNDC1 as disease contributing gene.
Acute otitis media (AOM) is among the most common pediatric diseases, and the most frequent reason for antibiotic treatment in children. Risk of AOM is dependent on environmental and host factors, as well as a significant genetic component. We identify genome-wide significance at a locus on 6q25.3 (rs2932989, Pmeta=2.15 × 10-09), and show that the associated variants are correlated with the methylation status of the FNDC1 gene (cg05678571, P=1.43 × 10-06), and further show it is an eQTL for FNDC1 (P=9.3 × 10-05). The mouse homologue, Fndc1, is expressed in middle ear tissue and its expression is upregulated upon lipopolysaccharide treatment. In this first GWAS of AOM and the largest OM genetic study to date, we identify the first genome-wide significant locus associated with AOM.
Department of Otolaryngology, Head and Neck Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000 CA, The Netherlands.|The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000 CA, The Netherlands.
Gijs
G
van Ingen
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Jin
J
Li
Department of Otolaryngology, Head and Neck Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000 CA, The Netherlands.
André
A
Goedegebure
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Rahul
R
Pandey
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Yun Rose
YR
Li
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Michael E
ME
March
The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000 CA, The Netherlands.|Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000 CA, The Netherlands.|Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000 CA, The Netherlands.
Vincent W V
VW
Jaddoe
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Marina
M
Bakay
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Frank D
FD
Mentch
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Kelly
K
Thomas
Department of Computer Science, New Jersey Institute of Technology, Newark 07102, New Jersey, USA.
Zhi
Z
Wei
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Xiao
X
Chang
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Heather S
HS
Hain
Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000 CA, The Netherlands.|Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000 CA, The Netherlands.
André G
AG
Uitterlinden
Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000 CA, The Netherlands.
Henriette A
HA
Moll
Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000 CA, The Netherlands.
Cornelia M
CM
van Duijn
Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000 CA, The Netherlands.|Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000 CA, The Netherlands.
Fernando
F
Rivadeneira
Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000 CA, The Netherlands.
Hein
H
Raat
Department of Otolaryngology, Head and Neck Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000 CA, The Netherlands.
Robert J
RJ
Baatenburg de Jong
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Patrick M
PM
Sleiman
Department of Otolaryngology, Head and Neck Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000 CA, The Netherlands.
Marc P
MP
van der Schroeff
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.|Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.|Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Hakon
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