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

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• 作者：Struan F.A. Grant ; Kai Wang ; Haitao Zhang ; Wendy Glaberson ; Kiran Annaiah ; Cecilia E. Kim ; Jonathan P. Bradfield ; Joseph T. Glessner ; Kelly A. Thomas ; Maria Garris ; Edward C. Frackelton ; F. George Otieno ; Rosetta M. Chiavacci ; Hyun-Duck Nah ; Richard E. Kirschner ; Hakon Hakonarson
• 刊名：The Journal of Pediatrics
• 出版年：2009
• 出版时间：December 2009
• 年：2009
• 卷：155
• 期：6
• 页码：909-913
• 全文大小：448 K

文摘

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 × 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.