A Genome-Wide Association Study Identifies a Locus for Nonsyndromic Cleft Lip with or without Cleft Palate on 8q24

作者：Grant Struan F A^*; Wang Kai; Zhang Haitao; Glaberson Wendy; Annaiah Kiran; Kim Cecilia E; Bradfield Jonathan P; Glessner Joseph T; Thomas Kelly A; Garris Maria; Frackelton Edward C; Otieno F George; Chiavacci Rosetta M; Nah Hyun Duck; Kirschner Richard E; Hakonarson Hakon

来源：Journal of Pediatrics, 2009, 155(6): 909-913.

DOI：10.1016/j.jpeds.2009.06.020

Objective To identify, in a non-hypothesis manner, novel genetic factors associated with nonsyndromic cleft lip with or without cleft palate (NSCL/P).
Study design 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 genomewide 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.

• 出版日期2009-12