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A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4
Journal article   Open access   Peer reviewed

A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4

Yah Huei Wu-Chou, Elizabeth W Pugh, Alan F Scott, Tao Wu, Alexandre R Vieira, Peadar N Kirke, Hong Wang, Shangzhi Huang, Anne M Molloy, Lina M Moreno, …
Nature genetics, Vol.42(6), pp.525-529
06/2010
DOI: 10.1038/ng.580
PMCID: PMC2941216
PMID: 20436469
url
http://hdl.handle.net/2262/75139View
Open Access

Abstract

Case-parent trios were used in a genome-wide association study of cleft lip with and without cleft palate. SNPs near two genes not previously associated with cleft lip with and without cleft palate (MAFB, most significant SNP rs13041247, with odds ratio (OR) per minor allele = 0.704, 95% CI 0.635-0.778, P = 1.44 × 10−11; and ABCA4, most significant SNP rs560426, with OR = 1.432, 95% CI 1.292-1.587, P = 5.01 × 10−12) and two previously identified regions (at chromosome 8q24 and IRF6) attained genome-wide significance. Stratifying trios into European and Asian ancestry groups revealed differences in statistical significance, although estimated effect sizes remained similar. Replication studies from several populations showed confirming evidence, with families of European ancestry giving stronger evidence for markers in 8q24, whereas Asian families showed stronger evidence for association with MAFB and ABCA4. Expression studies support a role for MAFB in palatal development.

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