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

Zhonglin Jia; Elizabeth J Leslie; Margaret E Cooper; Azeez Butali; Jennifer Standley; Jennifer Rigdon; Satoshi Suzuki; Ayana Gongorjav; T Enkhtur Shonkhuuz; Nagato Natsume; Bing Shi; Mary L Marazita; Jeffrey C Murray

doi:10.1002/ajmg.a.36912

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

Journal article

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

Zhonglin Jia, Elizabeth J Leslie, Margaret E Cooper, Azeez Butali, Jennifer Standley, Jennifer Rigdon, Satoshi Suzuki, Ayana Gongorjav, T Enkhtur Shonkhuuz, Nagato Natsume, …

American journal of medical genetics. Part A, Vol.167A(5), pp.1054-1060

05/2015

DOI: 10.1002/ajmg.a.36912

PMCID: PMC4402974

PMID: 25786657

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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.

Chromosomes, Human, Pair 13 - genetics

European Continental Ancestry Group - genetics

Genetic Predisposition to Disease

Genome-Wide Association Study

Humans

Asian Continental Ancestry Group - genetics

Male

Risk

Cleft Palate - genetics

Cleft Palate - physiopathology

Cleft Lip - genetics

Cleft Lip - physiopathology

Pedigree

Female

Polymorphism, Single Nucleotide

Details

Title: Subtitle: Replication of 13q31.1 association in nonsyndromic cleft lip with cleft palate in Europeans
Creators: Zhonglin Jia - Department of Cleft Lip and Palate Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Elizabeth J Leslie - Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
Margaret E Cooper - Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
Azeez Butali - Department of Oral Pathology, Radiology, and Medicine, College of Dentistry, University of Iowa, Iowa City, Iowa
Jennifer Standley - Department of Pediatrics, University of Iowa, Iowa City, Iowa
Jennifer Rigdon - Department of Pediatrics, University of Iowa, Iowa City, Iowa
Satoshi Suzuki - Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies, School of Dentistry, Aichi-Gakuin University, Japan
Ayana Gongorjav - National Center for Maternal and Child Health, Ulaanbaatar, Mongolia
T Enkhtur Shonkhuuz - National Center for Maternal and Child Health, Ulaanbaatar, Mongolia
Nagato Natsume - Division of Research and Treatment for Oral and Maxillofacial Congenital Anomalies, School of Dentistry, Aichi-Gakuin University, Japan
Bing Shi - Department of Cleft Lip and Palate Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Mary L Marazita - Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
Jeffrey C Murray - Department of Pediatrics, University of Iowa, Iowa City, Iowa
Resource Type: Journal article
Publication Details: American journal of medical genetics. Part A, Vol.167A(5), pp.1054-1060
DOI: 10.1002/ajmg.a.36912
PMID: 25786657
PMCID: PMC4402974
NLM abbreviation: Am J Med Genet A
ISSN: 1552-4825
eISSN: 1552-4833
Publisher: United States
Grant note: K99 DE022378 / NIDCR NIH HHS U01 DE20057 / NIDCR NIH HHS R00 DE022378 / NIDCR NIH HHS R01 DE016148 / NIDCR NIH HHS R37 DE008559 / NIDCR NIH HHS U01 DE020057 / NIDCR NIH HHS R37-DE08559 / NIDCR NIH HHS K99/R00-DE022378 / NIDCR NIH HHS
Language: English
Date published: 05/2015
Academic Unit: Oral Pathology, Radiology and Medicine; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
Record Identifier: 9984025360402771

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