title: Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24.
abstract: We conducted a genome-wide association study involving 224 cases and 383 controls of Central European origin to identify susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P). A 640-kb region at chromosome 8q24.21 was found to contain multiple markers with highly significant evidence for association with the cleft phenotype, including three markers that reached genome-wide significance. The 640-kb cleft-associated region was saturated with 146 SNP markers and then analyzed in our entire NSCL/P sample of 462 unrelated cases and 954 controls. In the entire sample, the most significant SNP (rs987525) had a P value of 3.34 x 10(-24). The odds ratio was 2.57 (95% CI = 2.02-3.26) for the heterozygous genotype and 6.05 (95% CI = 3.88-9.43) for the homozygous genotype. The calculated population attributable risk for this marker is 0.41, suggesting that this study has identified a major susceptibility locus for NSCL/P.
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Birnbaum
authors.forename: Kerstin U
authors.initials: KU
authors.lastname: Ludwig
authors.forename: Heiko
authors.initials: H
authors.lastname: Reutter
authors.forename: Stefan
authors.initials: S
authors.lastname: Herms
authors.forename: Michael
authors.initials: M
authors.lastname: Steffens
authors.forename: Michele
authors.initials: M
authors.lastname: Rubini
authors.forename: Carlotta
authors.initials: C
authors.lastname: Baluardo
authors.forename: Melissa
authors.initials: M
authors.lastname: Ferrian
authors.forename: Nilma
authors.initials: N
authors.lastname: Almeida de Assis
authors.forename: Margrieta A
authors.initials: MA
authors.lastname: Alblas
authors.forename: Sandra
authors.initials: S
authors.lastname: Barth
authors.forename: Jan
authors.initials: J
authors.lastname: Freudenberg
authors.forename: Carola
authors.initials: C
authors.lastname: Lauster
authors.forename: Gül
authors.initials: G
authors.lastname: Schmidt
authors.forename: Martin
authors.initials: M
authors.lastname: Scheer
authors.forename: Bert
authors.initials: B
authors.lastname: Braumann
authors.forename: Stefaan J
authors.initials: SJ
authors.lastname: Bergé
authors.forename: Rudolf H
authors.initials: RH
authors.lastname: Reich
authors.forename: Franziska
authors.initials: F
authors.lastname: Schiefke
authors.forename: Alexander
authors.initials: A
authors.lastname: Hemprich
authors.forename: Simone
authors.initials: S
authors.lastname: Pötzsch
authors.forename: Regine P
authors.initials: RP
authors.lastname: Steegers-Theunissen
authors.forename: Bernd
authors.initials: B
authors.lastname: Pötzsch
authors.forename: Susanne
authors.initials: S
authors.lastname: Moebus
authors.forename: Bernhard
authors.initials: B
authors.lastname: Horsthemke
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Kramer
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Wienker
authors.forename: Peter A
authors.initials: PA
authors.lastname: Mossey
authors.forename: Peter
authors.initials: P
authors.lastname: Propping
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Per
authors.initials: P
authors.lastname: Hoffmann
authors.forename: Michael
authors.initials: M
authors.lastname: Knapp
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mangold
mesh_terms: D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics; D005190:Family; D005260:Female; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D005858:Germany; D006720:Homozygote; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide