Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24.

Nat Genet 2009 Apr 8;41(4):473-7. Epub 2009 Mar 8.

Institute of Human Genetics, University of Bonn, Bonn, Germany.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1038/ng.333DOI Listing
April 2009
57 Reads

Publication Analysis

Top Keywords

lip cleft
8
cleft palate
8
nonsyndromic cleft
8
cleft lip
8
susceptibility locus
8
cleft
5
entire nscl/p
4
nscl/p sample
4
analyzed entire
4
snp markers
4
146 snp
4
sample 462
4
markers analyzed
4
462 unrelated
4
unrelated cases
4
cases 954
4
saturated 146
4
controls entire
4
954 controls
4
entire sample
4

References

(Supplied by CrossRef)

ML Marazita et al.
Am. J. Hum. Genet. 2004

A Jugessur et al.
Genet. Epidemiol. 2008

F Rahimov et al.
Nat. Genet. 2008

N Patterson et al.
PLoS Genet. 2006

D Reich et al.
Nat. Genet. 2008

KE Lohmueller et al.
Nat. Genet. 2003

T Becker et al.
Am. J. Hum. Genet. 2004

CR Weinberg et al.
Am. J. Hum. Genet. 1999

HM Cann et al.
Science 2002

A Sivertsen et al.
Br. Med. J. 2008

Similar Publications