Replication of Genome Wide Association Identified Candidate Genes Confirm the Role of Common and Rare Variants in PAX7 and VAX1 in the Etiology of Nonsyndromic CL(P)

Azeez Butali; Satoshi Suzuki; Margaret E Cooper; Adela M Mansilla; Karen Cuenco; Elizabeth J Leslie; Yasushi Suzuki; Teruyuki Niimi; Masahiko Yamamoto; Gongorjav Ayanga; Tudevdorj Erkhembaatar; Hiroo Furukawa; Kumiko Fujiwawa; Hideto Imura; Aline L Petrin; Nagato Natsume; Terri H Beaty; Mary L Marazita; Jeffery C Murray

doi:10.1002/ajmg.a.35749

Back

Replication of Genome Wide Association Identified Candidate Genes Confirm the Role of Common and Rare Variants in PAX7 and VAX1 in the Etiology of Nonsyndromic CL(P)

Journal article

Open access

Peer reviewed

Replication of Genome Wide Association Identified Candidate Genes Confirm the Role of Common and Rare Variants in PAX7 and VAX1 in the Etiology of Nonsyndromic CL(P)

Azeez Butali, Satoshi Suzuki, Margaret E Cooper, Adela M Mansilla, Karen Cuenco, Elizabeth J Leslie, Yasushi Suzuki, Teruyuki Niimi, Masahiko Yamamoto, Gongorjav Ayanga, …

American journal of medical genetics. Part A, Vol.161(5), pp.965-972

05/2013

DOI: 10.1002/ajmg.a.35749

PMCID: PMC3634899

PMID: 23463464

Files and links (1)

url

https://www.ncbi.nlm.nih.gov/pmc/articles/3634899View

Open Access

Abstract

Following recent genome wide association studies (GWAS), significant genetic associations have been identified for several genes with nonsyndromic cleft lip with or without cleft palate (CL(P)). To replicate two of these GWAS signals, we investigated the role of common and rare variants in the PAX7 and VAX1 genes. TaqMan genotyping was carried out for SNPs in VAX1 and PAX7 and transmission disequilibrium test (TDT) was performed to test for linkage and association in each population. Direct sequencing in and around the PAX7 and VAX1 genes in 1,326 individuals of European and Asian ancestry was done. The TDT analysis showed strong associations with markers in VAX1 (rs7078160, P = 2.7E−06 and rs475202, P = 0.0002) in a combined sample of Mongolian and Japanese CL(P) case–parent triads. Analyses using parent‐of‐origin effects showed significant excess transmission of the minor allele from both parents with the effect in the mothers (P = 6.5E−05, OR (transmission) = 1.91) more striking than in the fathers (P = 0.004, OR (transmission) = 1.67) for VAX1 marker rs7078160 in the combined Mongolian and Japanese samples when all cleft types were combined. The rs6659735 trinucleotide marker in PAX7 was significantly associated with all the US cleft groups combined (P = 0.007 in all clefts and P = 0.02 in CL(P)). Eight rare missense mutations found in PAX7 and two rare missense mutations in VAX1. Our study replicated previous GWAS findings for markers in VAX1 in the Asian population, and identified rare variants in PAX7 and VAX1 that may contribute to the etiology of CL(P). Determining the role of rare variants clearly warrants further investigation. © 2013 Wiley Periodicals, Inc.

GWAS

CL(P)

VAX1

PAX7

Details

Title: Subtitle: Replication of Genome Wide Association Identified Candidate Genes Confirm the Role of Common and Rare Variants in PAX7 and VAX1 in the Etiology of Nonsyndromic CL(P)
Creators: Azeez Butali - University of Iowa
Satoshi Suzuki - Aichi‐Gakuin University
Margaret E Cooper - School of Public Health, Johns Hopkins University
Adela M Mansilla - University of Iowa
Karen Cuenco - School of Public Health, Johns Hopkins University
Elizabeth J Leslie - University of Iowa
Yasushi Suzuki - School of Dentistry, Aichi‐Gakuin University
Teruyuki Niimi - School of Dentistry, Aichi‐Gakuin University
Masahiko Yamamoto - Aichi‐Gakuin University
Gongorjav Ayanga - Maternal and Children's Health Research Center Hospital
Tudevdorj Erkhembaatar - Maternal and Children's Health Research Center Hospital
Hiroo Furukawa - Aichi‐Gakuin University
Kumiko Fujiwawa - School of Dentistry, Aichi‐Gakuin University
Hideto Imura - School of Dentistry, Aichi‐Gakuin University
Aline L Petrin - University of Iowa
Nagato Natsume - School of Dentistry, Aichi‐Gakuin University
Terri H Beaty - School of Dental Medicine, Center for Craniofacial and Dental Genetics, University of Pittsburgh
Mary L Marazita - School of Public Health, University of Pittsburgh
Jeffery C Murray - College of Nursing, University of Iowa
Resource Type: Journal article
Publication Details: American journal of medical genetics. Part A, Vol.161(5), pp.965-972
DOI: 10.1002/ajmg.a.35749
PMID: 23463464
PMCID: PMC3634899
NLM abbreviation: Am J Med Genet A
ISSN: 1552-4825
eISSN: 1552-4833
Number of pages: 8
Grant note: National Institute for Dental and Craniofacial Research (NIH), Face Base Grant (K99‐DE022378‐01; R37‐DE08559 R01‐DE016148; U01‐DE‐018993; U01 DE‐20057) Aichi‐Gakuin (20791560)
Language: English
Date published: 05/2013
Academic Unit: Orthodontics; Oral Pathology, Radiology and Medicine; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research; Iowa Institute of Human Genetics
Record Identifier: 9984025336502771

Metrics

10 Record Views

55 Times Cited - Web of Science