Genome-wide association analyses identify variants in developmental genes associated with hypospadias

Frank Geller and colleagues report the results of a large genome-wide association study of hypospadias. They identify 18 susceptibility regions for this common congenital condition, many of which harbor genes important for embryonic development. Hypospadias is a common congenital condition in boys i...

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Veröffentlicht in:Nature genetics 2014-09, Vol.46 (9), p.957-963
Hauptverfasser: Geller, Frank, Feenstra, Bjarke, Carstensen, Lisbeth, Pers, Tune H, van Rooij, Iris A L M, Körberg, Izabella Baranowska, Choudhry, Shweta, Karjalainen, Juha M, Schnack, Tine H, Hollegaard, Mads V, Feitz, Wout F J, Roeleveld, Nel, Hougaard, David M, Hirschhorn, Joel N, Franke, Lude, Baskin, Laurence S, Nordenskjöld, Agneta, van der Zanden, Loes F M, Melbye, Mads
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container_end_page 963
container_issue 9
container_start_page 957
container_title Nature genetics
container_volume 46
creator Geller, Frank
Feenstra, Bjarke
Carstensen, Lisbeth
Pers, Tune H
van Rooij, Iris A L M
Körberg, Izabella Baranowska
Choudhry, Shweta
Karjalainen, Juha M
Schnack, Tine H
Hollegaard, Mads V
Feitz, Wout F J
Roeleveld, Nel
Hougaard, David M
Hirschhorn, Joel N
Franke, Lude
Baskin, Laurence S
Nordenskjöld, Agneta
van der Zanden, Loes F M
Melbye, Mads
description Frank Geller and colleagues report the results of a large genome-wide association study of hypospadias. They identify 18 susceptibility regions for this common congenital condition, many of which harbor genes important for embryonic development. Hypospadias 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 × 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.
doi_str_mv 10.1038/ng.3063
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subjects 45
45/43
45/88
631/208/205/2138
692/699/2768
Agriculture
Animal Genetics and Genomics
Biomedicine
Cancer Research
Case-Control Studies
Councils
Denmark
Development and progression
Embryonic growth stage
Female
Gene Function
Genes
Genes, Developmental
Genetic aspects
Genetic Predisposition to Disease
Genome-wide association studies
Genome-Wide Association Study - methods
Genomes
Genomics
Genotype
Human Genetics
Humans
Hypospadias
Hypospadias - genetics
Identification and classification
Male
Methods
Netherlands
Polymorphism, Single Nucleotide
Quantitative trait loci
Studies
Sweden
title Genome-wide association analyses identify variants in developmental genes associated with hypospadias
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