TY - JOUR
T1 - GWAS reveals new recessive loci associated with non-syndromic facial clefting
AU - Camargo, Mauricio
AU - Rivera, Dora
AU - Moreno, Lina
AU - Lidral, Andrew C.
AU - Harper, Ursula
AU - Jones, Marypat
AU - Solomon, Benjamin D.
AU - Roessler, Erich
AU - Vélez, Jorge I.
AU - Martinez, Ariel F.
AU - Chandrasekharappa, Settara C.
AU - Arcos-Burgos, Mauricio
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
KW - B3GAT1
KW - CSMD1
KW - Facial
KW - GWAS
KW - Non-syndromic clefting
KW - Recessive loci
UR - http://www.scopus.com/inward/record.url?scp=84866431873&partnerID=8YFLogxK
U2 - 10.1016/j.ejmg.2012.06.005
DO - 10.1016/j.ejmg.2012.06.005
M3 - Article
SN - 1769-7212
VL - 55
SP - 510
EP - 514
JO - European Journal of Medical Genetics
JF - European Journal of Medical Genetics
IS - 10
ER -