Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24.
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.
Birnbaum
Stefanie
S
Institute of Human Genetics, University of Bonn, Bonn, Germany.
Ludwig
Kerstin U
KU
Reutter
Heiko
H
Herms
Stefan
S
Steffens
Michael
M
Rubini
Michele
M
Baluardo
Carlotta
C
Ferrian
Melissa
M
Almeida de Assis
Nilma
N
Alblas
Margrieta A
MA
Barth
Sandra
S
Freudenberg
Jan
J
Lauster
Carola
C
Schmidt
Gül
G
Scheer
Martin
M
Braumann
Bert
B
Bergé
Stefaan J
SJ
Reich
Rudolf H
RH
Schiefke
Franziska
F
Hemprich
Alexander
A
Pötzsch
Simone
S
Steegers-Theunissen
Regine P
RP
Pötzsch
Bernd
B
Moebus
Susanne
S
Horsthemke
Bernhard
B
Kramer
Franz-Josef
FJ
Wienker
Thomas F
TF
Mossey
Peter A
PA
Propping
Peter
P
Cichon
Sven
S
Hoffmann
Per
P
Knapp
Michael
M
Nöthen
Markus M
MM
Mangold
Elisabeth
E
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