GWAS reveals new recessive loci associated with non-syndromic facial clefting

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• 作者：Mauricio Camargo ; Dora Rivera ; Lina Moreno ; Andrew C. Lidral ; Ursula Harper ; Marypat Jones ; Benjamin D. Solomon ; Erich Roessler ; Jorge I. V¨¦lez ; Ariel F. Martinez ; Settara C. Ch ; rasekharappa ; Mauricio Arcos-Burgos
• 关键词：Non-syndromic clefting ; Facial ; GWAS ; Recessive loci ; B3GAT1 ; CSMD1
• 刊名：European Journal of Medical Genetics
• 出版年：2012
• 出版时间：October, 2012
• 年：2012
• 卷：55
• 期：10
• 页码：510-514
• 全文大小：139 K

文摘

We have applied a GWAS to 40 consanguineous families segregating cases of non-syndromic cleft lip with or without cleft palate (NS CL/P) (a total of 160 affected and unaffected individuals) in order to trace potential recessive loci that confer susceptibility to this common facial malformation. Pedigree-based association test (PBAT) analyses reported nominal evidence of association and linkage over SNP markers located at 11q25 (rs4937877, P?=?2.7?¡Á?10^?6), 19p12 (rs4324267, P?=?1.6?¡Á?10^?5), 5q14.1 (rs4588572, P-value?=?3.36?¡Á?10^?5), and 15q21.1 (rs4774497, P?=?1.08?¡Á?10^?4). Using the Versatile Gene-Based Association Study to complement the PBAT results, we found clusters of markers located at chromosomes 19p12, 11q25, and 8p23.2 overcome the threshold for GWAS significance (P?<?1?¡Á?10^?7). From this study, new recessive loci implicated in NS CL/P include: B3GAT1, GLB1L2, ZNF431, ZNF714, and CSMD1, even though the functional association with the genesis of NS CL/P remains to be elucidated. These results emphasize the importance of using homogeneous populations, phenotypes, and family structures for GWAS combined with gene-based association analyses, and should encourage. other researchers to evaluate these genes on independent patient samples affected by NS CL/P.