A genome-wide association study identifies a locus for nonsyndromic cleft lip with or without cleft palate on 8q24.
OBJECTIVE
To identify, in a non-hypothesis manner, novel genetic factors associated with nonsyndromic cleft lip with or without cleft palate (NSCL/P).


METHODS
We performed a genome-wide association study in a pediatric cohort of European decent consisting of 111 NSCL/P cases and 5951 control subjects. All subjects were consecutively recruited from the Greater Philadelphia area from 2006 to 2009. High throughput genome-wide single nucleotide polymorphism genotyping was carried out with the Illumina Infinium II HumanHap550 BeadChip technology.


RESULTS
We observed association at the genome-wide significance level with SNP rs987525 at a locus on 8q24, which harbors no characterized genes to date (P = 9.18 x 10(-8); odds ratio = 2.09, 95% confidence interval = 1.59 to 2.76). While searching for a replication cohort, the same genetic determinant was established through a genome-wide association study of NSCL/P in Germany, so this previous report acts as a de novo replication for our independent observation outlined here.


CONCLUSIONS
These results strongly suggest that a locus on 8q24 is involved in the pathogenesis of NSCL/P.
Grant
Struan F A
SF
Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA 19104-4318, USA. grants@chop.edu
Wang
Kai
K
Zhang
Haitao
H
Glaberson
Wendy
W
Annaiah
Kiran
K
Kim
Cecilia E
CE
Bradfield
Jonathan P
JP
Glessner
Joseph T
JT
Thomas
Kelly A
KA
Garris
Maria
M
Frackelton
Edward C
EC
Otieno
F George
FG
Chiavacci
Rosetta M
RM
Nah
Hyun-Duck
HD
Kirschner
Richard E
RE
Hakonarson
Hakon
H
D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D002971:Cleft Lip / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*; D002972:Cleft Palate / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People / Q000235:genetics