Confirming genes influencing risk to cleft lip with/without cleft palate in a case-parent trio study

T H Beaty; M A Taub; A F Scott; J C Murray; M L Marazita; H Schwender; M M Parker; J B Hetmanski; P Balakrishnan; M A Mansilla; E Mangold; K U Ludwig; M M Noethen; M Rubini; N Elcioglu; I Ruczinski

doi:10.1007/s00439-013-1283-6

Back

Confirming genes influencing risk to cleft lip with/without cleft palate in a case-parent trio study

Journal article

Open access

Peer reviewed

Confirming genes influencing risk to cleft lip with/without cleft palate in a case-parent trio study

T H Beaty, M A Taub, A F Scott, J C Murray, M L Marazita, H Schwender, M M Parker, J B Hetmanski, P Balakrishnan, M A Mansilla, …

Human genetics, Vol.132(7), pp.771-781

07/2013

DOI: 10.1007/s00439-013-1283-6

PMCID: PMC3707506

PMID: 23512105

Files and links (1)

url

https://hdl.handle.net/11424/245750View

Open Access

Abstract

A collection of 1,108 case-parent trios ascertained through an isolated, non-syndromic cleft lip with or without cleft palate (CL/P) was used to replicate the findings from a genome-wide association study (GWAS) conducted by Beaty et al. (2010) where four different genes/regions were identified as influencing risk to CL/P. Tagging SNPs for 33 different genes were genotyped (1,269 SNPs). All four of the genes originally identified as showing genome-wide significance ( IRF6, ABCA4 and MAF , plus the 8q24 region) were confirmed in this independent sample of trios (who were primarily of European and Southeast Asian ancestry). In addition, eight genes classified as ‘second tier’ hits in the original study (PAX7, THADA, COL8A1/FILIP1L, DCAF4L2, GADD45G, NTN1, RBFOX3 and FOXE1 ) showed evidence of linkage and association in this replication sample. Meta-analysis between the original GWAS trios and these replication trios showed PAX7, COL8A1/FILIP1L and NTN1 achieved genome-wide significance. Tests for gene-environment interaction between these 33 genes and maternal smoking found evidence for interaction with two additional genes: GRID2 and ELAVL2 among European mothers (who had a higher rate of smoking than Asian mothers). Formal tests for gene-gene interaction (epistasis) failed to show evidence of statistical interaction in any simple fashion. This study confirms that many different genes influence risk to CL/P.

case-parent trios design

oral clefts

without cleft palate

Cleft lip with

birth defects

Details

Title: Subtitle: Confirming genes influencing risk to cleft lip with/without cleft palate in a case-parent trio study
Creators: T H Beaty - Department of Epidemiology, School of Public Health, Johns Hopkins University, 615 N Wolfe St., Baltimore MD 21205, USA
M A Taub - Department of Biostatistics, School of Public Health, Johns Hopkins University, 615 N Wolfe St., Baltimore MD 21205, USA
A F Scott - Institute of Genetic Medicine, School of Medicine, Johns Hopkins University, 600 N. Wolfe St., Baltimore MD 21205, USA
J C Murray - Department of Pediatrics, School of Medicine, University of Iowa, Iowa City IA 52242, USA
M L Marazita - Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Suite 500 Bridgeside Point, 100 Technology Dr., Pittsburgh PA 15219, USA
H Schwender - Mathematical Institute, Heinrich-Heine-University Duesseldorf, 40225 Duesseldorf, Germany
M M Parker - Department of Epidemiology, School of Public Health, Johns Hopkins University, 615 N Wolfe St., Baltimore MD 21205, USA
J B Hetmanski - Department of Epidemiology, School of Public Health, Johns Hopkins University, 615 N Wolfe St., Baltimore MD 21205, USA
P Balakrishnan - Department of Epidemiology, School of Public Health, Johns Hopkins University, 615 N Wolfe St., Baltimore MD 21205, USA
M A Mansilla - Department of Pediatrics, School of Medicine, University of Iowa, Iowa City IA 52242, USA
E Mangold - Institute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany
K U Ludwig - Institute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany
M M Noethen - Institute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany
M Rubini - Medical Genetics Unit, Department of Biomedical and Special Surgery Sciences, University of Ferrara, Via Fossato di Mortara 74, I-44121 Ferrara, Italy
N Elcioglu - Department of Pediatric Genetics, School of Medicine, Marmara University, Istanbul 34 890 Turkey
I Ruczinski - Department of Biostatistics, School of Public Health, Johns Hopkins University, 615 N Wolfe St., Baltimore MD 21205, USA
Resource Type: Journal article
Publication Details: Human genetics, Vol.132(7), pp.771-781
DOI: 10.1007/s00439-013-1283-6
PMID: 23512105
PMCID: PMC3707506
NLM abbreviation: Hum Genet
ISSN: 0340-6717
eISSN: 1432-1203
Grant note: P60 DE013076 || DE / National Institute of Dental and Craniofacial Research : NIDCR R01 DE014581 || DE / National Institute of Dental and Craniofacial Research : NIDCR U01 DE018993 || DE / National Institute of Dental and Craniofacial Research : NIDCR
Language: English
Date published: 07/2013
Academic Unit: 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: 9984025456302771

Metrics

15 Record Views

120 Times Cited - Web of Science

See more details