Genome-wide association study identifies a new susceptibility locus for cleft lip with or without a cleft palate

被引：165

作者：

Sun, Yimin ^{[1
,2
,3
,4
]}

Huang, Yongqing ^{[5
,6
]}

Yin, Aihua ^{[7
,8
,9
]}

Pan, Yongchu ^{[10
,11
,12
]}

Wang, Yirui ^{[1
,3
,4
]}

Wang, Cheng ^{[12
,13
]}

Du, Yong ^{[5
,6
]}

Wang, Meilin ^{[14
]}

Lan, Feifei ^{[7
,8
,9
]}

Hu, Zhibin ^{[12
,13
]}

Wang, Guoqing ^{[3
,4
]}

Jiang, Min ^{[5
,6
]}

Ma, Junqing ^{[10
,11
]}

Zhang, Xiaozhuang ^{[15
]}

Ma, Hongxia ^{[12
,13
]}

Ma, Jian ^{[5
,6
]}

Zhang, Weibing ^{[10
,11
]}

Huang, Qun ^{[16
]}

Zhou, Zhongwei ^{[5
,6
]}

Ma, Lan ^{[10
,11
]}

Li, Yadi ^{[5
,6
]}

Jiang, Hongbing ^{[10
,17
]}

Xie, Lan ^{[1
]}

Jiang, Yuyang ^{[2
]}

Shi, Bing ^{[18
,19
]}

Cheng, Jing ^{[3
,4
]}

Shen, Hongbing ^{[12
,13
]}

Wang, Lin ^{[10
,11
,12
]}

Yang, Yinxue ^{[5
,6
]}

机构：

[1] Tsinghua Univ, Med Syst Biol Res Ctr, Sch Med, Dept Biomed Engn, Beijing 100084, Peoples R China

[2] Tsinghua Univ, Grad Sch Shenzhen, State Key Lab Breeding Base Shenzhen, Key Lab Chem Biol, Shenzhen 518055, Peoples R China

[3] CapitalBio Corp, Beijing 102206, Peoples R China

[4] Natl Engn Res Ctr Beijing Biochip Technol, Beijing 102206, Peoples R China

[5] Ningxia Med Univ, Gen Hosp, Yinchuan 750004, Peoples R China

[6] Natl Engn Res Ctr Beijing Biochip Technol, Sub Ctr Ningxia, Yinchuan 750004, Peoples R China

[7] Guangdong Women & Children Hosp, Ctr Med Genet, Guangzhou 511442, Guangdong, Peoples R China

[8] Guangdong Women & Children Hosp, Maternal & Children Metab Genet Key Lab, Guangzhou 511442, Guangdong, Peoples R China

[9] Biobank Guangdong Women & Children Hosp, Guangzhou 511442, Guangdong, Peoples R China

[10] Nanjing Med Univ, Jiangsu Key Lab Oral Dis, Nanjing 210029, Jiangsu, Peoples R China

[11] Nanjing Med Univ, Affiliated Hosp Stomatol, Dept Orthodont, Nanjing 210029, Jiangsu, Peoples R China

[12] Nanjing Med Univ, State Key Lab Reprod Med, Nanjing 210029, Jiangsu, Peoples R China

[13] Nanjing Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Nanjing 210029, Jiangsu, Peoples R China

[14] Nanjing Med Univ, Sch Publ Hlth, Dept Genet Toxicol, Key Lab Modern Toxicol,Minist Educ, Nanjing 210029, Jiangsu, Peoples R China

[15] Guangdong Women & Children Hosp, Thalassemia Diag Ctr, Guangzhou 511442, Guangdong, Peoples R China

[16] Guangdong Women & Children Hosp, Dept Dent, Guangzhou 511442, Guangdong, Peoples R China

[17] Nanjing Med Univ, Affiliated Hosp Stomatol, Dept Oral & Maxillofacial Surg, Nanjing 210029, Jiangsu, Peoples R China

[18] Sichuan Univ, State Key Lab Oral Dis, Chengdu 610041, Peoples R China

[19] Sichuan Univ, West China Coll Stomatol, Chengdu 610041, Peoples R China

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

基金：

中国国家自然科学基金;

关键词：

RUBINSTEIN-TAYBI SYNDROME; POPULATION-BASED COHORT; FOCAL ADHESION KINASE; CREBBP GENE; RISK; VARIANTS; ENHANCERS; TWINS; VAX1; SRC;

D O I：

10.1038/ncomms7414

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：

Nonsyndromic cleft lip with or without a cleft palate (NSCL/P) is among the most common human congenital birth defects and imposes a substantial physical and financial burden on affected individuals. Here, we conduct a case-control-based GWAS followed by two rounds of replication; we include six independent cohorts from China to elucidate the genetic architecture of NSCL/P in Chinese populations. Using this combined analysis, we identify a new locus at 16p13.3 associated with NSCL/P: rs8049367 between CREBBP and ADCY9 (odds ratio = 0.74, P = 8.98 x 10(-12)). We confirm that the reported loci at 1q32.2, 10q25.3, 17p13.1 and 20q12 are also involved in NSCL/P development in Chinese populations. Our results provide additional evidence that the rs2235371-related haplotype at 1q32.2 could play a more important role than the previously identified causal variant rs642961 in Chinese populations. These findings provide information on the genetic basis and mechanisms of NSCL/P.

引用

页数：7

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