A genome-wide association study identifies two risk loci for congenital heart malformations in Han Chinese populations

Zhibin Hu, Yongyong Shi, Xuming Mo, Jing Xu, Bijun Zhao, Yuan Lin, Shiwei Yang, Zhengfeng Xu, Juncheng Dai, Shandong Pan, Min Da, Xiaowei Wang, Bo Qian, Yang Wen, Juan Wen, Jinliang Xing, Xuejiang Guo, Yankai Xia, Hongxia Ma, Guangfu Jin & 7 others Shiqiang Yu, Jiayin Liu, Zuomin Zhou, Xinru Wang, Yijiang Chen, Jiahao Sha, Hongbing Shen

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Congenital heart malformation (CHM) is the most common form of congenital human birth anomaly and is the leading cause of infant mortality. Although some causative genes have been identified, little progress has been made in identifying genes in which low-penetrance susceptibility variants occur in the majority of sporadic CHM cases. To identify common genetic variants associated with sporadic non-syndromic CHM in Han Chinese populations, we performed a multistage genome-wide association study (GWAS) in a total of 4,225 CHM cases and 5,112 non-CHM controls. The GWAS stage included 945 cases and 1,246 controls and was followed by 2-stage validation with 2,160 cases and 3,866 controls. The combined analyses identified significant associations (P < 5.0 × 10 -8) at 1p12 (rs2474937 near TBX15; odds ratio (OR) = 1.40; P = 8.44 × 10 -10) and 4q31.1 (rs1531070 in MAML3; OR = 1.40; P = 4.99 × 10 -12). These results extend current knowledge of genetic contributions to CHM in Han Chinese populations.

Original languageEnglish (US)
Pages (from-to)818-821
Number of pages4
JournalNature Genetics
Volume45
Issue number7
DOIs
StatePublished - Jul 1 2013
Externally publishedYes

Fingerprint

Congenital Heart Defects
Genome-Wide Association Study
Population
Odds Ratio
Penetrance
Infant Mortality
Genes
Parturition

ASJC Scopus subject areas

  • Genetics

Cite this

A genome-wide association study identifies two risk loci for congenital heart malformations in Han Chinese populations. / Hu, Zhibin; Shi, Yongyong; Mo, Xuming; Xu, Jing; Zhao, Bijun; Lin, Yuan; Yang, Shiwei; Xu, Zhengfeng; Dai, Juncheng; Pan, Shandong; Da, Min; Wang, Xiaowei; Qian, Bo; Wen, Yang; Wen, Juan; Xing, Jinliang; Guo, Xuejiang; Xia, Yankai; Ma, Hongxia; Jin, Guangfu; Yu, Shiqiang; Liu, Jiayin; Zhou, Zuomin; Wang, Xinru; Chen, Yijiang; Sha, Jiahao; Shen, Hongbing.

In: Nature Genetics, Vol. 45, No. 7, 01.07.2013, p. 818-821.

Research output: Contribution to journalArticle

Hu, Z, Shi, Y, Mo, X, Xu, J, Zhao, B, Lin, Y, Yang, S, Xu, Z, Dai, J, Pan, S, Da, M, Wang, X, Qian, B, Wen, Y, Wen, J, Xing, J, Guo, X, Xia, Y, Ma, H, Jin, G, Yu, S, Liu, J, Zhou, Z, Wang, X, Chen, Y, Sha, J & Shen, H 2013, 'A genome-wide association study identifies two risk loci for congenital heart malformations in Han Chinese populations', Nature Genetics, vol. 45, no. 7, pp. 818-821. https://doi.org/10.1038/ng.2636
Hu, Zhibin ; Shi, Yongyong ; Mo, Xuming ; Xu, Jing ; Zhao, Bijun ; Lin, Yuan ; Yang, Shiwei ; Xu, Zhengfeng ; Dai, Juncheng ; Pan, Shandong ; Da, Min ; Wang, Xiaowei ; Qian, Bo ; Wen, Yang ; Wen, Juan ; Xing, Jinliang ; Guo, Xuejiang ; Xia, Yankai ; Ma, Hongxia ; Jin, Guangfu ; Yu, Shiqiang ; Liu, Jiayin ; Zhou, Zuomin ; Wang, Xinru ; Chen, Yijiang ; Sha, Jiahao ; Shen, Hongbing. / A genome-wide association study identifies two risk loci for congenital heart malformations in Han Chinese populations. In: Nature Genetics. 2013 ; Vol. 45, No. 7. pp. 818-821.
@article{2474c2413a224840b4afaa6e745451ec,
title = "A genome-wide association study identifies two risk loci for congenital heart malformations in Han Chinese populations",
abstract = "Congenital heart malformation (CHM) is the most common form of congenital human birth anomaly and is the leading cause of infant mortality. Although some causative genes have been identified, little progress has been made in identifying genes in which low-penetrance susceptibility variants occur in the majority of sporadic CHM cases. To identify common genetic variants associated with sporadic non-syndromic CHM in Han Chinese populations, we performed a multistage genome-wide association study (GWAS) in a total of 4,225 CHM cases and 5,112 non-CHM controls. The GWAS stage included 945 cases and 1,246 controls and was followed by 2-stage validation with 2,160 cases and 3,866 controls. The combined analyses identified significant associations (P < 5.0 × 10 -8) at 1p12 (rs2474937 near TBX15; odds ratio (OR) = 1.40; P = 8.44 × 10 -10) and 4q31.1 (rs1531070 in MAML3; OR = 1.40; P = 4.99 × 10 -12). These results extend current knowledge of genetic contributions to CHM in Han Chinese populations.",
author = "Zhibin Hu and Yongyong Shi and Xuming Mo and Jing Xu and Bijun Zhao and Yuan Lin and Shiwei Yang and Zhengfeng Xu and Juncheng Dai and Shandong Pan and Min Da and Xiaowei Wang and Bo Qian and Yang Wen and Juan Wen and Jinliang Xing and Xuejiang Guo and Yankai Xia and Hongxia Ma and Guangfu Jin and Shiqiang Yu and Jiayin Liu and Zuomin Zhou and Xinru Wang and Yijiang Chen and Jiahao Sha and Hongbing Shen",
year = "2013",
month = "7",
day = "1",
doi = "10.1038/ng.2636",
language = "English (US)",
volume = "45",
pages = "818--821",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - A genome-wide association study identifies two risk loci for congenital heart malformations in Han Chinese populations

AU - Hu, Zhibin

AU - Shi, Yongyong

AU - Mo, Xuming

AU - Xu, Jing

AU - Zhao, Bijun

AU - Lin, Yuan

AU - Yang, Shiwei

AU - Xu, Zhengfeng

AU - Dai, Juncheng

AU - Pan, Shandong

AU - Da, Min

AU - Wang, Xiaowei

AU - Qian, Bo

AU - Wen, Yang

AU - Wen, Juan

AU - Xing, Jinliang

AU - Guo, Xuejiang

AU - Xia, Yankai

AU - Ma, Hongxia

AU - Jin, Guangfu

AU - Yu, Shiqiang

AU - Liu, Jiayin

AU - Zhou, Zuomin

AU - Wang, Xinru

AU - Chen, Yijiang

AU - Sha, Jiahao

AU - Shen, Hongbing

PY - 2013/7/1

Y1 - 2013/7/1

N2 - Congenital heart malformation (CHM) is the most common form of congenital human birth anomaly and is the leading cause of infant mortality. Although some causative genes have been identified, little progress has been made in identifying genes in which low-penetrance susceptibility variants occur in the majority of sporadic CHM cases. To identify common genetic variants associated with sporadic non-syndromic CHM in Han Chinese populations, we performed a multistage genome-wide association study (GWAS) in a total of 4,225 CHM cases and 5,112 non-CHM controls. The GWAS stage included 945 cases and 1,246 controls and was followed by 2-stage validation with 2,160 cases and 3,866 controls. The combined analyses identified significant associations (P < 5.0 × 10 -8) at 1p12 (rs2474937 near TBX15; odds ratio (OR) = 1.40; P = 8.44 × 10 -10) and 4q31.1 (rs1531070 in MAML3; OR = 1.40; P = 4.99 × 10 -12). These results extend current knowledge of genetic contributions to CHM in Han Chinese populations.

AB - Congenital heart malformation (CHM) is the most common form of congenital human birth anomaly and is the leading cause of infant mortality. Although some causative genes have been identified, little progress has been made in identifying genes in which low-penetrance susceptibility variants occur in the majority of sporadic CHM cases. To identify common genetic variants associated with sporadic non-syndromic CHM in Han Chinese populations, we performed a multistage genome-wide association study (GWAS) in a total of 4,225 CHM cases and 5,112 non-CHM controls. The GWAS stage included 945 cases and 1,246 controls and was followed by 2-stage validation with 2,160 cases and 3,866 controls. The combined analyses identified significant associations (P < 5.0 × 10 -8) at 1p12 (rs2474937 near TBX15; odds ratio (OR) = 1.40; P = 8.44 × 10 -10) and 4q31.1 (rs1531070 in MAML3; OR = 1.40; P = 4.99 × 10 -12). These results extend current knowledge of genetic contributions to CHM in Han Chinese populations.

UR - http://www.scopus.com/inward/record.url?scp=84879694320&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879694320&partnerID=8YFLogxK

U2 - 10.1038/ng.2636

DO - 10.1038/ng.2636

M3 - Article

VL - 45

SP - 818

EP - 821

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 7

ER -