Genome-wide association study identifies new disease loci for isolated clubfoot

Tian Xiao Zhang, Gabe Haller, Peng Lin, David M. Alvarado, Jacqueline T. Hecht, Susan H. Blanton, B. Stephens Richards, John P. Rice, Matthew B. Dobbs, Christina A. Gurnett

Research output: Contribution to journalArticle

13 Scopus citations

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.

Original languageEnglish
Pages (from-to)334-339
Number of pages6
JournalJournal of Medical Genetics
Volume51
Issue number5
DOIs
StatePublished - Jan 1 2014

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