Journal article
Genome-wide association analyses identify variants in developmental genes associated with hypospadias
Statens Serum Institut1
Massachusetts General Hospital/Harvard Medical School2
Karolinska Institutet3
Stanford University4
Department of Systems Biology, Technical University of Denmark5
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark6
Boston Children's Hospital7
Broad Institute of Harvard University and Massachusetts Institute of Technology8
Radboud University Nijmegen9
Karolinska University Hospital10
University of California at San Diego11
University of Groningen12
...and 2 moreHypospadias is a common congenital condition in boys in which the urethra opens on the underside of the penis. We performed a genome-wide association study on 1,006 surgery-confirmed hypospadias cases and 5,486 controls from Denmark. After replication genotyping of an additional 1,972 cases and 1,812 controls from Denmark, the Netherlands and Sweden, 18 genomic regions showed independent association with P <5 x 10(-8).
Together, these loci explain 9% of the liability to developing this condition. Several of the identified regions harbor genes with key roles in embryonic development (including HOXA4, IRX5, IRX6 and EYA1). Subsequent pathway analysis with GRAIL and DEPICT provided additional insight into possible genetic mechanisms causing hypospadias.
| Language: | English |
|---|---|
| Publisher: | Nature Publishing Group |
| Year: | 2014 |
| Pages: | 957-967 |
| ISSN: | 15461718 and 10614036 |
| Types: | Journal article |
| DOI: | 10.1038/ng.3063 |
| ORCIDs: | 0000-0003-0207-4831 and 0000-0001-8264-6785 |
03502, Genetics - General 03508, Genetics - Human 15504, Urinary system - Physiology and biochemistry 15506, Urinary system - Pathology 16504, Reproductive system - Physiology and biochemistry 16506, Reproductive system - Pathology 25503, Development and Embryology - Pathology Biochemistry and Molecular Biophysics Chemical Coordination and Homeostasis DEPICT DIFFERENTIATION DISEASE Denmark Europe Palearctic region EXPRESSION GENETICS GRAIL Genetic aspects HYPOSPADIAS IDENTIFICATION LOCI METAANALYSIS MUTATIONS Molecular Genetics Netherlands Europe Palearctic region POPULATION Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] human common female, male RISK Reproduction Reproductive System SDG 3 - Good Health and Well-being SUSCEPTIBILITY Urinary System genome-wide association analyses laboratory techniques, genetic techniques human EYA1 gene [Hominidae] expression human HOXA4 gene [Hominidae] expression human IRX5 gene [Hominidae] expression human IRX6 gene [Hominidae] expression hypospadias Hypospadias (MeSH) urologic disease, reproductive system disease/female, reproductive system disease/male, congenital disease penis reproductive system surgery therapeutic and prophylactic techniques, clinical techniques urethra reproductive system, excretory system
