TY - JOUR
T1 - Genome-wide association study identifies new disease loci for isolated clubfoot
AU - Zhang, Tian Xiao
AU - Haller, Gabe
AU - Lin, Peng
AU - Alvarado, David M.
AU - Hecht, Jacqueline T.
AU - Blanton, Susan H.
AU - Richards, B. Stephens
AU - Rice, John P.
AU - Dobbs, Matthew B.
AU - Gurnett, Christina A.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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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U2 - 10.1136/jmedgenet-2014-102303
DO - 10.1136/jmedgenet-2014-102303
M3 - Article
C2 - 24667120
AN - SCOPUS:84899487432
SN - 0022-2593
VL - 51
SP - 334
EP - 339
JO - Journal of medical genetics
JF - Journal of medical genetics
IS - 5
ER -