Identification of novel susceptibility loci for non-syndromic cleft lip with or without cleft palate.
Identification of novel susceptibility loci for non-syndromic cleft lip with or without cleft palate.
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DOI：
10.1111/jcmm.15878
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发表时间：
2020-12
影响因子：
5.3
通讯作者：
Pan Y
中科院分区：
文献类型：
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作者：
Ma L;Lou S;Miao Z;Yao S;Yu X;Kan S;Zhu G;Yang F;Zhang C;Zhang W;Wang M;Wang L;Pan Y
虽然已经报道了几个非综合征性唇裂伴或不伴腭裂（NSCL/P）的全基因组关联研究（GWAS），但仍有更多新的关联信号有待开发。在这里，我们对我们先前发表的中国GWAS队列研究进行了深入分析，该研究在一个额外的dbGaP病例-父母三人组和另一个内部南京队列中进行了复制，并最终确定了五个新的显著关联信号（rs 11119445：SERTAD 4的3'端，P = 6.44 × 10−14; rs 227227和rs 12561877：SYT 14的内含子，P分别为5.02 × 10−13和2.80 × 10−11; rs643118：TRAF 3 IP 3内含子，P = 4.45 × 10−6; rs 2095293：NR 6A 1内含子，P = 2.98 × 10−5）。来自这些SNP的加权遗传风险评分（wGRS）的平均值（标准差）在NSCL/P病例中为1.83（0.65），在对照组中为1.58（0.68）（P = 2.67 × 10−16）。Rs643118被确定为亚洲人和欧洲人中NSCL/P的共同易感因素，而rs 227227可能与NSCL/P以及NSCPO的风险有关。此外，与对照胚胎相比，sertad 4敲低斑马鱼模型导致sox 2下调，并导致心脏周围水肿和下颌骨缺陷。总之，这项研究提高了我们对NSCL/P遗传易感性的认识，并为中国人群中NSCL/P的病因学提供了进一步的线索。
Although several genome‐wide association studies (GWAS) of non‐syndromic cleft lip with or without cleft palate (NSCL/P) have been reported, more novel association signals are remained to be exploited. Here, we performed an in‐depth analysis of our previously published Chinese GWAS cohort study with replication in an extra dbGaP case‐parent trios and another in‐house Nanjing cohort, and finally identified five novel significant association signals (rs11119445: 3’ of SERTAD4, P = 6.44 × 10−14; rs227227 and rs12561877: intron of SYT14, P = 5.02 × 10−13 and 2.80 × 10−11, respectively; rs643118: intron of TRAF3IP3, P = 4.45 × 10−6; rs2095293: intron of NR6A1, P = 2.98 × 10−5). The mean (standard deviation) of the weighted genetic risk score (wGRS) from these SNPs was 1.83 (0.65) for NSCL/P cases and 1.58 (0.68) for controls, respectively (P = 2.67 × 10−16). Rs643118 was identified as a shared susceptible factor of NSCL/P among Asians and Europeans, while rs227227 may contribute to the risk of NSCL/P as well as NSCPO. In addition, sertad4 knockdown zebrafish models resulted in down‐regulation of sox2 and caused oedema around the heart and mandibular deficiency, compared with control embryos. Taken together, this study has improved our understanding of the genetic susceptibility to NSCL/P and provided further clues to its aetiology in the Chinese population.
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影响因子：
3.7
作者：
Kobayashi GS;Alvizi L;Sunaga DY;Francis-West P;Kuta A;Almada BV;Ferreira SG;de Andrade-Lima LC;Bueno DF;Raposo-Amaral CE;Menck CF;Passos-Bueno MR
通讯作者：
Passos-Bueno MR
影响因子：
5.3
作者：
Beaty, T. H.;Taub, M. A.;Scott, A. F.;Murray, J. C.;Marazita, M. L.;Schwender, H.;Parker, M. M.;Hetmanski, J. B.;Balakrishnan, P.;Mansilla, M. A.;Mangold, E.;Ludwig, K. U.;Noethen, M. M.;Rubini, M.;Elcioglu, N.;Ruczinski, I.
通讯作者：
Ruczinski, I.
影响因子：
3.5
作者：
Bennetts, Jennifer S.;Fowles, Lindsay F.;Wicking, Carol
通讯作者：
Wicking, Carol
pre-miR-146a 基因的功能多态性与非综合征性口面裂的风险相关
影响因子：
3.9
作者：
Pan, Yongchu;Li, Dandan;Wang, Lin
通讯作者：
Wang, Lin
影响因子：
30.8
作者：
通讯作者：
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