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

Mauricio Camargo, Dora Rivera, Lina Moreno, Andrew C. Lidral, Ursula Harper, Marypat Jones, Benjamin D. Solomon, Erich Roessler, Jorge I. Vélez, Ariel F. Martinez, Settara C. Chandrasekharappa, Mauricio Arcos-Burgos*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    31 Citations (Scopus)

    Abstract

    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 × 10-6), 19p12 (rs4324267, P = 1.6 × 10-5), 5q14.1 (rs4588572, P-value = 3.36 × 10-5), and 15q21.1 (rs4774497, P = 1.08 × 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 × 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.

    Original languageEnglish
    Pages (from-to)510-514
    Number of pages5
    JournalEuropean Journal of Medical Genetics
    Volume55
    Issue number10
    DOIs
    Publication statusPublished - Oct 2012

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