Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24
Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24
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DOI：
10.1038/ng.333
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发表时间：
2009-04-01
期刊：
影响因子：
30.8
通讯作者：
Mangold, Elisabeth
中科院分区：
文献类型：
--
作者：
Birnbaum, Stefanie;Ludwig, Kerstin U.;Mangold, Elisabeth
我们进行了一项全基因组关联研究，涉及中欧血统的224例病例和383例对照，以确定非综合征性唇裂伴或不伴腭裂（NSCL/P）的易感基因。发现染色体8q24.21处的640-kb区域包含多个标记，这些标记具有与裂缝表型相关的高度显著的证据，包括三个达到全基因组意义的标记。640 kb的裂缝相关区域饱和146个SNP标记，然后在我们的整个NSCL/P样本的462个无关的情况下和954对照进行分析。在整个样本中，最显著的SNP（rs 987525）的P值为3.34 x 10（-24）。杂合子基因型和纯合子基因型的优势比分别为2.57（95%CI = 2.02-3.26）和6.05（95%CI = 3.88-9.43）。该标记物的人群归因危险度为0.41，表明本研究已确定了NSCL/P的主要易感基因座。
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.