Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24

被引:362
作者
Birnbaum, Stefanie [1 ,2 ]
Ludwig, Kerstin U. [3 ]
Reutter, Heiko [1 ]
Herms, Stefan [3 ]
Steffens, Michael [4 ]
Rubini, Michele [5 ]
Baluardo, Carlotta [5 ]
Ferrian, Melissa [5 ]
de Assis, Nilma Almeida [1 ]
Alblas, Margrieta A. [3 ]
Barth, Sandra [3 ]
Freudenberg, Jan [6 ]
Lauster, Carola [7 ]
Schmidt, Guel [7 ]
Scheer, Martin [8 ]
Braumann, Bert [9 ]
Berge, Stefaan J. [10 ]
Reich, Rudolf H. [11 ]
Schiefke, Franziska [12 ]
Hemprich, Alexander [12 ]
Poetzsch, Simone [13 ]
Steegers-Theunissen, Regine P. [14 ]
Poetzsch, Bernd [15 ]
Moebus, Susanne [16 ]
Horsthemke, Bernhard [17 ]
Kramer, Franz-Josef [2 ]
Wienker, Thomas F. [4 ]
Mossey, Peter A. [18 ]
Propping, Peter
Cichon, Sven [1 ,3 ]
Hoffmann, Per [1 ,3 ]
Knapp, Michael [4 ]
Noethen, Markus M. [1 ,3 ]
Mangold, Elisabeth [1 ]
机构
[1] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany
[2] Univ Gottingen, Dept Oral & Maxillofacial Surg, Gottingen, Germany
[3] Univ Bonn, Life & Brain Ctr, Dept Genom, D-5300 Bonn, Germany
[4] Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-5300 Bonn, Germany
[5] Univ Ferrara, Dept Expt & Diagnost Med, Med Genet Unit, I-44100 Ferrara, Italy
[6] Northshore LIJ Univ Hosp, Feinstein Inst Med Res, Ctr Genom & Human Genet, New York, NY USA
[7] Humboldt Univ, Dept Cleft Lip & Cleft Palate Surg, Berlin, Germany
[8] Univ Cologne, Dept Oral & Maxillofacial Surg, Cologne, Germany
[9] Univ Cologne, Dept Orthodont, Cologne, Germany
[10] Radboud Univ Nijmegen, Dept Oral & Maxillofacial Surg, NL-6525 ED Nijmegen, Netherlands
[11] Univ Bonn, Dept Oral & Maxillofacial Plast Surg, D-5300 Bonn, Germany
[12] Univ Leipzig, Dept Oral & Maxillofacial Surg, Leipzig, Germany
[13] Univ Magdeburg, D-39106 Magdeburg, Germany
[14] Univ Med Ctr, Rotterdam, Netherlands
[15] Univ Bonn, Inst Expt Hematol & Transfus Med, D-5300 Bonn, Germany
[16] Univ Duisburg Essen, Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Duisburg, Germany
[17] Univ Duisburg Essen, Univ Hosp Essen, Inst Human Genet, Duisburg, Germany
[18] Univ Dundee, Dent Hosp & Sch, Orthodont Unit, Dundee, Scotland
关键词
GENOME-WIDE ASSOCIATION; GENETIC-VARIANTS; EXPRESSION; RISK; IRF6; METAANALYSIS; DISEASE; DESIGN; CANCER; SCAN;
D O I
10.1038/ng.333
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
We conducted a genome-wide association study involving 224 cases and 383 controls of Central European origin to identify susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P). A 640-kb region at chromosome 8q24.21 was found to contain multiple markers with highly significant evidence for association with the cleft phenotype, including three markers that reached genome-wide significance. The 640-kb cleft-associated region was saturated with 146 SNP markers and then analyzed in our entire NSCL/P sample of 462 unrelated cases and 954 controls. In the entire sample, the most significant SNP (rs987525) had a P value of 3.34 x 10(-24). The odds ratio was 2.57 (95% CI = 2.02-3.26) for the heterozygous genotype and 6.05 (95% CI = 3.88-9.43) for the homozygous genotype. The calculated population attributable risk for this marker is 0.41, suggesting that this study has identified a major susceptibility locus for NSCL/P.
引用
收藏
页码:473 / 477
页数:5
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