Send to

Choose Destination
Am J Med Genet A. 2015 May;167A(5):1054-1060. doi: 10.1002/ajmg.a.36912. Epub 2015 Mar 18.

Replication of 13q31.1 association in nonsyndromic cleft lip with cleft palate in Europeans.

Author information

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Department of Pediatrics, University of Iowa, Iowa City, Iowa.
Department of Cleft Lip and Palate Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Department of Oral Pathology, Radiology, and Medicine, College of Dentistry, University of Iowa, Iowa City, Iowa.
Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies, School of Dentistry, Aichi-Gakuin University, Japan.
National Center for Maternal and Child Health, Ulaanbaatar, Mongolia.
Contributed equally


Genome wide association (GWA) studies have successfully identified at least a dozen loci associated with orofacial clefts. However, these signals may be unique to specific populations and require replication to validate and extend findings as a prelude to etiologic SNP discovery. We attempted to replicate the findings of a recent meta-analysis of orofacial cleft GWA studies using four different ancestral populations. We studied 946 pedigrees (3,436 persons) of European (US white and Danish) and Asian (Japanese and Mongolian) origin. We genotyped six SNPs that represented the most significant P-value associations identified in published studies: rs742071 (1p36), rs7590268 (2p21), rs7632427 (3p11.1), rs12543318 (8q21.3), rs8001641 (13q31.1), and rs7179658 (15q22.2). We directly sequenced three non-coding conserved regions 200 kb downstream of SPRY2 in 713 cases, 438 controls, and 485 trios from the US, Mongolia, and the Philippines. We found rs8001641 to be significantly associated with nonsyndromic cleft lip with cleft palate (NSCLP) in Europeans (P-value = 4 × 10(-5), ORtransmission = 1.86 with 95% confidence interval: 1.38-2.52). We also found several novel sequence variants in the conserved regions in Asian and European samples, which may help to localize common variants contributing directly to the risk for NSCLP. This study confirms the prior association between rs8001641 and NSCLP in European populations.


GWA study; SPRY2; nonsyndromic orofacial clefting; replication

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center