X-linked markers in the Duchenne muscular dystrophy gene associated with oral clefts
Poorav J. Patel ; Terri H. Beaty ; Alan F. Scott ; Bing Shi ; Sun H. Jee ; Samuel Chong ; Vincent Yeow ; Xiaoqian Ye ; Hong Wang ; Yah-Huei Wu-Chou ; Rolv T. Lie ; Sheng C. Jin ; Richard J. Redett ; Margaret Rose ; Tanda Murray ; Tao Wu ; Jacqueline B. Hetmanski ; Ronald G. Munger ; Mary L. Marazita ; Jeffrey C. Murray ; Ingo Ruczinski
European Journal of Oral Sciences, Vol.121(2) : 63~68, 2013
European Journal of Oral Sciences
As part of an international consortium, case-parent trios were collected for a genome-wide association study of isolated, non-syndromic oral clefts, including cleft lip (CL), cleft palate (CP), and cleft lip and palate (CLP). Non-syndromic oral clefts have a complex and heterogeneous etiology. Risk is influenced by genes and environmental factors, and differs markedly by gender. Family-based association tests (FBAT) were used on 14,486 single nucleotide polymorphisms (SNPs) spanning the X chromosome, stratified by type of cleft and racial group. Significant results, even after multiple-comparisons correction, were obtained for the Duchenne muscular dystrophy (DMD) gene, the largest single gene in the human genome, among CL/P (i.e., both CL and CLP combined) trios. When stratified into groups of European and Asian ancestry, stronger signals were obtained for Asian subjects. Although conventional sliding-window haplotype analysis showed no increase in significance, selected combinations of the 25 most significant SNPs in the DMD gene identified four SNPs together that attained genome-wide significance among Asian CL/P trios, raising the possibility of interaction between distant SNPs within the DMD gene.