title: Replication of 13q31.1 association in nonsyndromic cleft lip with cleft palate in Europeans.
abstract: 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.
authors: 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.
authors: Zhonglin
authors: Z
authors: Jia
authors: Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Elizabeth J
authors: EJ
authors: Leslie
authors: Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Margaret E
authors: ME
authors: Cooper
authors: Department of Oral Pathology, Radiology, and Medicine, College of Dentistry, University of Iowa, Iowa City, Iowa.
authors: Azeez
authors: A
authors: Butali
authors: Department of Pediatrics, University of Iowa, Iowa City, Iowa.
authors: Jennifer
authors: J
authors: Standley
authors: Department of Pediatrics, University of Iowa, Iowa City, Iowa.
authors: Jennifer
authors: J
authors: Rigdon
authors: Department of Pediatrics, University of Iowa, Iowa City, Iowa.|Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies, School of Dentistry, Aichi-Gakuin University, Japan.
authors: Satoshi
authors: S
authors: Suzuki
authors: National Center for Maternal and Child Health, Ulaanbaatar, Mongolia.
authors: Ayana
authors: A
authors: Gongorjav
authors: National Center for Maternal and Child Health, Ulaanbaatar, Mongolia.
authors: T Enkhtur
authors: TE
authors: Shonkhuuz
authors: Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies, School of Dentistry, Aichi-Gakuin University, Japan.
authors: Nagato
authors: N
authors: Natsume
authors: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|Department of Cleft Lip and Palate Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors: Bing
authors: B
authors: Shi
authors: Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Mary L
authors: ML
authors: Marazita
authors: Department of Pediatrics, University of Iowa, Iowa City, Iowa.
authors: Jeffrey C
authors: JC
authors: Murray
mesh_terms: D044466:Asian People / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics* / Q000503:physiopathology; D002972:Cleft Palate / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D044465:White People / Q000235:genetics
keywords: GWA study; SPRY2; nonsyndromic orofacial clefting; replication