Craniofacial microsomia (CFM) is a rare congenital anomaly that involves immature derivatives from the first and second pharyngeal arches. The genetic pathogenesis of CFM is still unclear. Here we interrogate 0.9 million genetic variants in 939 CFM cases and 2,012 controls from China. After genotyping of an additional 443 cases and 1,669 controls, we identify 8 significantly associated loci with the most significant SNP rs13089920 (logistic regression P = 2.15 x 10(-120)) and 5 suggestive loci. The above 13 associated loci, harboured by candidates of ROBO1, GATA3, GBX2, FGF3, NRP2, EDNRB, SHROOM3, SEMA7A, PLCD3, KLF12 and EPAS1, are found to be enriched for genes involved in neural crest cell (NCC) development and vasculogenesis. We then perform whole-genome sequencing on 21 samples from the case cohort, and identify several novel loss-of-function mutations within the associated loci. Our results provide new insights into genetic background of craniofacial microsomia.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [31201006, 31371347, 81372085, 81571924, 81300863]
第一作者机构：[1]Chinese Acad Sci, Beijing 100101, Peoples R China;[2]Chinese Acad Sci, Key Lab Genome Sci & Informat, Beijing Inst Genom, Beijing 100101, Peoples R China;[3]Chinese Acad Med Sci, Plast Surg Hosp, Dept Ear Reconstruct, Beijing 100144, Peoples R China;
通讯作者：
通讯机构：[1]Chinese Acad Sci, Beijing 100101, Peoples R China;[2]Chinese Acad Sci, Key Lab Genome Sci & Informat, Beijing Inst Genom, Beijing 100101, Peoples R China;[3]Chinese Acad Med Sci, Plast Surg Hosp, Dept Ear Reconstruct, Beijing 100144, Peoples R China;
推荐引用方式(GB/T 7714)：
Zhang Yong-Biao,Hu Jintian,Zhang Jiao,et al.Genome-wide association study identifies multiple susceptibility loci for craniofacial microsomia[J].NATURE COMMUNICATIONS.2016,7:-.doi:10.1038/ncomms10605.
APA：
Zhang, Yong-Biao,Hu, Jintian,Zhang, Jiao,Zhou, Xu,Li, Xin...&Zhang, Qingguo.(2016).Genome-wide association study identifies multiple susceptibility loci for craniofacial microsomia.NATURE COMMUNICATIONS,7,
MLA：
Zhang, Yong-Biao,et al."Genome-wide association study identifies multiple susceptibility loci for craniofacial microsomia".NATURE COMMUNICATIONS 7.(2016):-
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