Genetic Determinants of Facial Clefting: Analysis of 357 Candidate Genes Using Two National Cleft Studies from Scandinavia

• DOI: 10.1371/journal.pone.0005385
• Publication Date: 2009-04-28T19:58:01Z
• Authors: Astanand Jugessur; Min Shi; Håkon Kristian Gj...; Rolv Terje Lie; Allen James Wilcox; Clarice Ring Wein...; Kaare Christensen; Abee Lowman Boyles; Sandra Daack-Hirsch; Truc Nguyen Trung; Camilla Bille; Andrew Carl Lidral; Jeffrey Clark Murray
• Keywords: Candidate gene; Genetic Association; SNP

Background Facial clefts are common birth defects with a strong genetic component. To identify fetal risk factors for clefting, 1536 SNPs in 357 candidate genes were genotyped two population-based samples from Scandinavia (Norway: 562 case-parent and 592 control-parent triads; Denmark: 235 triads). Methodology/Principal Findings We used complementary statistical methods, TRIMM HAPLIN, to look associations across these national samples. tests association each gene by using multi-SNP genotypes triads directly without the need infer haplotypes. HAPLIN on other hand estimates full haplotype distribution over set of relative risks associated haplotype. For isolated cleft lip or palate (I-CL/P), both identified significant IRF6 ADH1C populations, but only found an FGF12. (I-CP), ALX3, MKX, PDGFC was HAPLIN. In addition, ETV5 that not detected TRIMM. Conclusion/Significance Strong seven replicated Scandinavian our approach effectively strongest previously known clefting—with IRF6. Based cohorts similar ancestry, robust methods large panel most promising date, this study unknown clefting provides additional candidates analytic approaches advance field.