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Published on: August 15, 2019
Genome-wide association study identifies new disease loci for isolated clubfoot
Tian-Xiao Zhang1, Gabe Haller, Peng Lin
1Division of Biology and Biomedical Sciences, Washington University School of Medicine, St Louis, Missouri, USA.
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.
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