Replication of 13q31.1 association in nonsyndromic cleft lip with cleft palate in Europeans.
Replication of 13q31.1 association in nonsyndromic cleft lip with cleft palate in Europeans.
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DOI：
10.1002/ajmg.a.36912
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发表时间：
2015-05
影响因子：
2
通讯作者：
Murray, Jeffrey C.
中科院分区：
文献类型：
--
作者：
Jia, Zhonglin;Leslie, Elizabeth J.;Cooper, Margaret E.;Butali, Azeez;Standley, Jennifer;Rigdon, Jennifer;Suzuki, Satoshi;Gongorjav, Ayana;Shonkhuuz, T. Enkhtur;Natsume, Nagato;Shi, Bing;Marazita, Mary L.;Murray, Jeffrey C.
全基因组关联（GWA）研究已成功识别出至少十几个与口颌裂相关的基因座。然而，这些信号可能是特定人群所独有的，需要复制来验证和扩展研究结果，作为病因 SNP 发现的前奏。我们试图使用四个不同的祖先群体来复制最近对口面裂 GWA 研究进行荟萃分析的结果。我们研究了欧洲（美国白人和丹麦）和亚洲（日本和蒙古）血统的 946 个血统（3436 人）。我们对代表已发表研究中确定的最显着 P 值关联的 6 个 SNP 进行了基因分型：rs742071 (1p36)、rs7590268 (2p21)、rs7632427 (3p11.1)、rs12543318 (8q21.3)、rs8001641 (13q31.1) 和rs7179658 (15q22.2)。我们直接对来自美国、蒙古和菲律宾的 713 个病例、438 个对照和 485 个三人组中 SPRY2 下游 200kb 的三个非编码保守区进行了测序。我们发现 rs8001641 与欧洲人的唇裂伴腭裂 (NSCLP) 显着相关（p 值=4 × 10−5，ORtransmission=1.86，95% 置信区间：1.38-2.52）。我们还在亚洲和欧洲样本的保守区域发现了几种新的序列变异，这可能有助于定位直接导致 NSCLP 风险的常见变异。这项研究证实了欧洲人群中 rs8001641 与 NSCLP 之间的先前关联。
Genome wide association (GWA) studies have successfully identified at least a dozen loci associated with orofacial clefts. However, these signals may be unique to specific populations and require replication to validate and extend findings as a prelude to etiologic SNP discovery. We attempted to replicate the findings of a recent meta-analysis of orofacial cleft GWA studies using four different ancestral populations. We studied 946 pedigrees (3436 persons) of European (US white and Danish) and Asian (Japanese and Mongolian) origin. We genotyped six SNPs which represented the most significant P value associations identified in published studies: rs742071 (1p36), rs7590268 (2p21), rs7632427 (3p11.1), rs12543318 (8q21.3), rs8001641 (13q31.1) and rs7179658 (15q22.2). We directly sequenced three non-coding conserved regions 200kb downstream of SPRY2 in 713 cases, 438 controls, and 485 trios from the US, Mongolia, and the Philippines. We found rs8001641 to be significantly associated with cleft lip with cleft palate (NSCLP) in Europeans (p-value=4 × 10−5, ORtransmission=1.86 with 95% confidence interval: 1.38-2.52). We also found several novel sequence variants in the conserved regions in Asian and European samples, which may help to localize common variants contributing directly to the risk for NSCLP. This study confirms the prior association between rs8001641 and NSCLP in European populations.
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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