Genome-wide association study identifies multiple susceptibility loci for craniofacial microsomia

被引：78

作者：

Zhang, Yong-Biao ^{[1
,2
,3
]}

Hu, Jintian ^{[3
]}

Zhang, Jiao ^{[3
,4
]}

Zhou, Xu ^{[3
]}

Li, Xin ^{[5
]}

Gu, Chaohao ^{[1
,2
]}

Liu, Tun ^{[3
]}

Xie, Yangchun ^{[3
]}

Liu, Jiqiang ^{[6
]}

Gu, Mingliang ^{[1
,2
]}

Wang, Panpan ^{[1
,2
]}

Wu, Tingting ^{[1
,2
]}

Qian, Jin ^{[3
]}

Wang, Yue ^{[3
]}

Dong, Xiaoqun ^{[7
]}

Yu, Jun ^{[1
,2
]}

Zhang, Qingguo ^{[3
]}

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

[4] E Carolina Univ, Brody Sch Med, Dept Anat & Cell Biol, Greenville, NC 27834 USA

[5] Capital Univ Med Sci, Beijing Anzhen Hosp, Dept Cardiol, Beijing 100029, Peoples R China

[6] Beijing KPS Biotechnol, Beijing 102206, Peoples R China

[7] Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Internal Med, Oklahoma City, OK 73104 USA

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

中国国家自然科学基金;

关键词：

GROWTH-FACTOR; MICROTIA; MORPHOGENESIS; VISUALIZATION; DISRUPTION; EFFICIENT; GENETICS; RECEPTOR; VARIANTS; DEFECTS;

D O I：

10.1038/ncomms10605

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：9

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