title: Genome-wide association study identifies new disease loci for isolated clubfoot.
abstract: BACKGROUND
  Clubfoot is a common congenital birth defect with complex inheritance patterns. Currently, the genetic and morphological basis of clubfoot is poorly understood. To identify genetic risk factors associated with clubfoot, we performed a genome-wide association study of common genetic variants.
  
  
  METHODS
  The DNA of 396 isolated clubfoot patients and 1000 controls of European descent was genotyped for >600 000 single nucleotide polymorphisms (SNP) using the Affymetrix 6.0 array. Replication was performed with an independent cohort of 370 isolated clubfoot cases and 363 controls of European descent.
  
  
  RESULTS
  Strongest evidence for an association of clubfoot was found with an intergenic SNP on chromosome 12q24.31 between NCOR2 and ZNF664 (rs7969148, OR=0.58, p=1.25×10⁻⁵) that was significant on replication (combined OR=0.63, p=1.90×10⁻⁷). Additional suggestive SNPs were identified near FOXN3, SORCS1 and MMP7/TMEM123 that also confirmed on replication.
  
  
  CONCLUSIONS
  Our study suggests a potential role for common genetic variation in several genes that have not previously been implicated in clubfoot pathogenesis.
authors.affiliation: Division of Biology and Biomedical Sciences, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Tian-Xiao
authors.initials: TX
authors.lastname: Zhang
authors.forename: Gabe
authors.initials: G
authors.lastname: Haller
authors.forename: Peng
authors.initials: P
authors.lastname: Lin
authors.forename: David M
authors.initials: DM
authors.lastname: Alvarado
authors.forename: Jacqueline T
authors.initials: JT
authors.lastname: Hecht
authors.forename: Susan H
authors.initials: SH
authors.lastname: Blanton
authors.forename: B
authors.initials: B
authors.lastname: Stephens Richards
authors.forename: John P
authors.initials: JP
authors.lastname: Rice
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Dobbs
authors.forename: Christina A
authors.initials: CA
authors.lastname: Gurnett
mesh_terms: D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics; D002881:Chromosomes, Human, Pair 12; D003025:Clubfoot / Q000235:genetics*; D051858:Forkhead Transcription Factors; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000235:genetics; D056985:Nuclear Receptor Co-Repressor 2 / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; C106158:FOXN3 protein, human; D051858:Forkhead Transcription Factors; C539130:NCOR2 protein, human; D056985:Nuclear Receptor Co-Repressor 2; D011956:Receptors, Cell Surface; D012097:Repressor Proteins; C472780:SORCS1 protein, human; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7
keywords: clubfoot; genome wide association study; transcription factor