Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease

Lu, Xiangfeng; Wang, Laiyuan; Chen, Shufeng; He, Lin; Yang, Xueli; Shi, Yongyong; Cheng, Jing; Zhang, Liang; Gu, C. Charles; Huang, Jianfeng; Wu, Tangchun; Ma, Yun; Li, Jianxin; Cao, Jie; Chen, Jichun; Ge, Dongliang; Fan, Zhongjie; Liu, Ying; Zhao, Liancheng; Li, Hongfan; Zhou, Xiaoyang; Chen, Lan‐Ying; Liu, Donghua; Chen, Jingping; Duan, Xin; Hao, Yongchen; Wang, Ligui; Lu, Fanghong; Liu, Zhendong; Yao, Cailiang; Shen, Chong; Pu, Xiaodong; Yu, Lin; Fang, Xianghua; Xu, Lizhen; Mu, Jianjun; Wu, Xianping; Ruan, Zheng; Wu, Na‐Qiong; Zhao, Qi; Li, Yun; Liu, Xiaoli; Wang, Mengqin; Yu, Dahai; Hu, Dongsheng; Xu, Jun‐Fa; Guo, Dongshuang; Sun, Dongling; Wang, Qianqian; Yang, Ying; Liu, Fangchao; Mao, Qunxia; Liang, Xiaohua; Ji, Jingfeng; Chen, Panpan; Mo, Xing‐Bo; Li, Dianjiang; Chai, Guoping; Tang, Yi‐Da; Li, Xiangdong; Du, Zhenhan; Li, Xuehui; Dou, Chenlong; Yang, Zidong; Meng, Qingwei; Wang, Dong; Wang, Renping; Yang, Jun; Schunkert, Heribert; Samani, Nilesh J.; Kathiresan, Sekar; Reilly, Muredach P.; Erdmann, Jeanette; Peng, Xiaozhong; Wu, Xigui; Liu, Depei; Yang, Yuejin; Chen, Runsheng; Qiang, Boqin; Gu, Dongfeng

doi:10.1038/ng.2337

Cited by 292 publications

(224 citation statements)

References 40 publications

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“…(B) The number of SNP s detected with genome‐wide significance after replication correlates with the number of individuals included in the discovery studies. Symbols denote the numbers of genotyped SNP s [dots: ≤ 500,000 SNP s (Samani et al , 2007; McPherson et al , 2007; Helgadottir et al , 2007; Myocardial Infarction Genetics Consortium, 2009; Erdmann et al , 2009; Tregouet et al , 2009; IBC 50K CAD Consortium, 2011; Lu et al , 2012); asterisks: 2,500,000 SNP s (Coronary Artery Disease C4D Genetics Consortium, 2011; Schunkert et al , 2011; CARDIoGRAMplusC4D Consortium et al , 2013); arrow: 940,000 SNP s (Nikpay et al , 2015)].…”

Section: Genome‐wide Association Studies In Coronary Artery Disease Amentioning

confidence: 99%

The impact of genome‐wide association studies on the pathophysiology and therapy of cardiovascular disease

2016

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Cardiovascular diseases are leading causes for death worldwide. Genetic disposition jointly with traditional risk factors precipitates their manifestation. Whereas the implications of a positive family history for individual risk have been known for a long time, only in the past few years have genome‐wide association studies (GWAS) shed light on the underlying genetic variations. Here, we review these studies designed to increase our understanding of the pathophysiology of cardiovascular diseases, particularly coronary artery disease and myocardial infarction. We focus on the newly established pathways to exemplify the translation from the identification of risk‐related genetic variants to new preventive and therapeutic strategies for cardiovascular disease.

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Section: Genome‐wide Association Studies In Coronary Artery Disease Amentioning

confidence: 99%

The impact of genome‐wide association studies on the pathophysiology and therapy of cardiovascular disease

2016

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“…In 2007, three groups independently reported the first region of the genome to be linked to CAD utilizing the GWAS approach (46)(47)(48) Chinese, Korean, or Japanese subjects, with at least 6 of these loci overlapping with loci uncovered in Europeans (63)(64)(65)(66)(67). Thus, both ethnic-specific as well as cross-ethnic loci have been uncovered to date.…”

Section: Discovery Of the First Locus Predisposing To Common Presentamentioning

confidence: 99%

Genetics: Implications for Prevention and Management of Coronary Artery Disease

Assimes

Roberts

2016

Journal of the American College of Cardiology

103

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An exciting new era has dawned for the prevention and management of CAD utilizing genetic risk variants. The recent identification of over 60 susceptibility loci for coronary artery disease (CAD) confirm not only the importance of established risk factors, but also the existence of many novel causal pathways that are expected to improve our understanding of the genetic basis of CAD and facilitate the development of new therapeutic agents over time. Concurrently, Mendelian randomization studies have provided intriguing insights on the causal relationship between CAD-related traits, and highlight the potential benefits of long-term modifications of risk factors. Lastly, genetic risk scores of CAD may serve not only as prognostic, but also as predictive markers and carry the potential to considerably improve the delivery of established prevention strategies. This review will summarize the evolution and discovery of genetic risk variants for CAD and their current and future clinical applications. Key Words: genetic variation, Mendelian randomization, risk scores, sequencingAbbreviations and Acronyms CAD = coronary artery disease GRS = genetic risk score GWAS = genome-wide association study HDL = high-density lipoprotein LDL = low-density lipoprotein MI = myocardial infarction MR = Mendelian randomization SNP = single-nucleotide polymorphism WES = whole-exome sequencing WGS = whole-genome sequencing 3

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“…3 Even after large-scale genome-wide association studies (GWAS) in European populations, GWAS in Asian populations have identified novel loci. [4][5][6][7] More additional loci are certainly left unidentified, and in such a situation, it remains elusive in total how many susceptibility loci exist. Here, to potently identify as many susceptibility loci as possible, GWAS and replication studies in a total of 44 673 Japanese participants were performed.…”

Section: Introductionmentioning

confidence: 99%

A genome-wide association study identifies PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for myocardial infarction in Japanese

et al. 2014

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Despite considerable progress in preventive and therapeutic strategies, myocardial infarction (MI) is one of the leading causes of death throughout the world. A total of 55 susceptibility genes have been identified mostly in European genome-wide association studies (GWAS). Nevertheless, large-scale GWAS from other population could possibly find additional susceptibility loci. To identify as many MI susceptibility loci as possible, we performed a large-scale genomic analysis in Japanese population. To identify MI susceptibility loci in Japanese, we conducted a GWAS using 1666 cases and 3198 controls using the Illumina Human610-Quad BeadChip and HumanHap550v3 Genotyping BeadChip. We performed replication studies using a total of 11 412 cases and 28 397 controls in the Japanese population. Our study identified two novel susceptibility loci for MI: PLCL2 on chromosome 3p24.3 (rs4618210:A4G, P ¼ 2.60 Â 10 À9 , odds ratio (OR) ¼ 0.91) and AP3D1-DOT1L-SF3A2 on chromosome 19p13.3 (rs3803915:A4C, P ¼ 3.84 Â 10 À9 , OR ¼ 0.89). Besides, a total of 14 previously reported MI susceptibility loci were replicated in our study. In particular, we validated a strong association on chromosome 12q24 (rs3782886:A4G: P ¼ 1.14 Â 10 À14 , OR ¼ 1.46). Following pathway analysis using 265 genes related to MI or coronary artery disease, we found that these loci might be involved in the pathogenesis of MI via the promotion of atherosclerosis. In the present large-scale genomic analysis, we identified PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for MI in the Japanese population. Our findings will add novel findings for MI susceptibility loci. INTRODUCTIONMyocardial infarction (MI), the severest form of coronary artery disease (CAD), is characterized by the occlusion of the coronary artery, resulting in ischemic damage of the myocardium. The occlusion of the coronary artery is characterized by abrupt plaque rupture with thrombogenesis 1 following the atherosclerotic process, which has recently been regarded as a chronic inflammatory condition involving lipid accumulation, abnormal extracellular matrix metabolism, innate immunity with macrophages, and the adaptive immune response with T and B lymphocytes. 2 Despite recent dramatic advances in preventive and/or therapeutic strategies, MI is still one of the leading causes of death in Asian populations as well as European populations.The pathogenesis of MI is considered to be the cumulative effect of multiple genetic and environmental factors. For the genetic aspect, a

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Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease

Cited by 292 publications

References 40 publications

The impact of genome‐wide association studies on the pathophysiology and therapy of cardiovascular disease

The impact of genome‐wide association studies on the pathophysiology and therapy of cardiovascular disease

Genetics: Implications for Prevention and Management of Coronary Artery Disease

A genome-wide association study identifies PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for myocardial infarction in Japanese

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