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

10 Citations (Scopus)

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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Clubfoot
Genome-Wide Association Study
Single Nucleotide Polymorphism
Inheritance Patterns
Chromosomes
DNA

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Zhang, T. X., Haller, G., Lin, P., Alvarado, D. M., Hecht, J. T., Blanton, S. H., ... Gurnett, C. A. (2014). Genome-wide association study identifies new disease loci for isolated clubfoot. Journal of Medical Genetics, 51(5), 334-339. https://doi.org/10.1136/jmedgenet-2014-102303

Genome-wide association study identifies new disease loci for isolated clubfoot. / Zhang, Tian Xiao; Haller, Gabe; Lin, Peng; Alvarado, David M.; Hecht, Jacqueline T.; Blanton, Susan H; Richards, B. Stephens; Rice, John P.; Dobbs, Matthew B.; Gurnett, Christina A.

In: Journal of Medical Genetics, Vol. 51, No. 5, 01.01.2014, p. 334-339.

Research output: Contribution to journalArticle

Zhang, TX, Haller, G, Lin, P, Alvarado, DM, Hecht, JT, Blanton, SH, Richards, BS, Rice, JP, Dobbs, MB & Gurnett, CA 2014, 'Genome-wide association study identifies new disease loci for isolated clubfoot', Journal of Medical Genetics, vol. 51, no. 5, pp. 334-339. https://doi.org/10.1136/jmedgenet-2014-102303
Zhang, Tian Xiao ; Haller, Gabe ; Lin, Peng ; Alvarado, David M. ; Hecht, Jacqueline T. ; Blanton, Susan H ; Richards, B. Stephens ; Rice, John P. ; Dobbs, Matthew B. ; Gurnett, Christina A. / Genome-wide association study identifies new disease loci for isolated clubfoot. In: Journal of Medical Genetics. 2014 ; Vol. 51, No. 5. pp. 334-339.
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