Format

Send to

Choose Destination
J Med Genet. 2014 May;51(5):334-9. doi: 10.1136/jmedgenet-2014-102303. Epub 2014 Mar 25.

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

Author information

1
Division of Biology and Biomedical Sciences, Washington University School of Medicine, St Louis, Missouri, USA.

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.

KEYWORDS:

clubfoot; genome wide association study; transcription factor

PMID:
24667120
DOI:
10.1136/jmedgenet-2014-102303
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center