Joint Effects of Genetic Variants in Multiple Loci on the Risk of Coronary Artery Disease in Chinese Han Subjects

Background: The aim of the present study was to explore risk variants for coronary artery disease (CAD) and to evaluate their joint effects (quantified by genetic risk score; GRS) on the discrimination of CAD in a Chinese Han sample. Methods and Results: An association analysis of 91 single nucleoti...

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Veröffentlicht in:Circulation Journal 2012, Vol.76(8), pp.1987-1992
Hauptverfasser: Lv, Xiaofei, Zhang, Yuan, Rao, Shaoqi, Qiu, Jian, Wang, Min, Luo, Xiaoqin, Zuo, Xiaoyu, Su, Dongfang, Feng, Xiang, Yang, Yan, Ouyang, Ping, Chen, Yibing, Li, Xinrui, Xiao, Yunjun, Ling, Wenhua
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container_end_page 1992
container_issue 8
container_start_page 1987
container_title Circulation Journal
container_volume 76
creator Lv, Xiaofei
Zhang, Yuan
Rao, Shaoqi
Qiu, Jian
Wang, Min
Luo, Xiaoqin
Zuo, Xiaoyu
Su, Dongfang
Feng, Xiang
Yang, Yan
Ouyang, Ping
Chen, Yibing
Li, Xinrui
Xiao, Yunjun
Ling, Wenhua
description Background: The aim of the present study was to explore risk variants for coronary artery disease (CAD) and to evaluate their joint effects (quantified by genetic risk score; GRS) on the discrimination of CAD in a Chinese Han sample. Methods and Results: An association analysis of 91 single nucleotide polymorphisms (SNPs) with CAD risk was undertaken in 1,007 CAD patients and 889 healthy controls. Two GRSs, counted GRS (cGRS) and weighted GRS (wGRS), were calculated using the significant SNPs, and their discriminant power for CAD was assessed using receiver-operating characteristic (ROC) curve analysis. Eight SNPs (rs11206510, rs10118757, rs2383206, rs501120, rs2075292, rs174547, rs173539, and rs255052) were nominally significantly associated with CAD (P
doi_str_mv 10.1253/circj.CJ-12-0156
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Methods and Results: An association analysis of 91 single nucleotide polymorphisms (SNPs) with CAD risk was undertaken in 1,007 CAD patients and 889 healthy controls. Two GRSs, counted GRS (cGRS) and weighted GRS (wGRS), were calculated using the significant SNPs, and their discriminant power for CAD was assessed using receiver-operating characteristic (ROC) curve analysis. Eight SNPs (rs11206510, rs10118757, rs2383206, rs501120, rs2075292, rs174547, rs173539, and rs255052) were nominally significantly associated with CAD (P&lt;0.05), and 5 of them were newly reported. The GRSs derived from the 8 SNPs improved the discrimination of CAD compared to that using 4 conventional risk factors (P=0.002 for cGRS and P=0.009 for wGRS). After 10-fold cross-validation 100 times, the average areas under the curve were 0.668 (95% confidence interval [CI]: 0.667-0.669), 0.686 (95% CI: 0.685-0.687) and 0.690 (95% CI: 0.689-0.691) for models with conventional risk factors only, conventional risk factors plus cGRS, and conventional risk factors plus wGRS, respectively. Conclusions: A multigenic GRS, generated by combining multiple gene variants, can improve discrimination of CAD, thereby confirming the joint effects of these gene variants on CAD in this Chinese Han population.  (Circ J 2012; 76: 1987–1992)</description><identifier>ISSN: 1346-9843</identifier><identifier>EISSN: 1347-4820</identifier><identifier>DOI: 10.1253/circj.CJ-12-0156</identifier><identifier>PMID: 22664640</identifier><language>eng</language><publisher>Japan: The Japanese Circulation Society</publisher><subject>Aged ; Asian Continental Ancestry Group ; China - epidemiology ; Coronary artery disease ; Coronary Artery Disease - epidemiology ; Coronary Artery Disease - genetics ; Female ; Genetic Loci ; Genetic risk score ; Genetic variants ; Humans ; Joint effect ; Male ; Middle Aged ; Multifactorial Inheritance ; Polymorphism, Single Nucleotide ; Risk Factors ; ROC Curve</subject><ispartof>Circulation Journal, 2012, Vol.76(8), pp.1987-1992</ispartof><rights>2012 THE JAPANESE CIRCULATION SOCIETY</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c595t-ef18c137d9c506d2f8c96fb10670d496911d601501da1b13186752d9225ba3b13</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22664640$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lv, Xiaofei</creatorcontrib><creatorcontrib>Zhang, Yuan</creatorcontrib><creatorcontrib>Rao, Shaoqi</creatorcontrib><creatorcontrib>Qiu, Jian</creatorcontrib><creatorcontrib>Wang, Min</creatorcontrib><creatorcontrib>Luo, Xiaoqin</creatorcontrib><creatorcontrib>Zuo, Xiaoyu</creatorcontrib><creatorcontrib>Su, Dongfang</creatorcontrib><creatorcontrib>Feng, Xiang</creatorcontrib><creatorcontrib>Yang, Yan</creatorcontrib><creatorcontrib>Ouyang, Ping</creatorcontrib><creatorcontrib>Chen, Yibing</creatorcontrib><creatorcontrib>Li, Xinrui</creatorcontrib><creatorcontrib>Xiao, Yunjun</creatorcontrib><creatorcontrib>Ling, Wenhua</creatorcontrib><title>Joint Effects of Genetic Variants in Multiple Loci on the Risk of Coronary Artery Disease in Chinese Han Subjects</title><title>Circulation Journal</title><addtitle>Circ J</addtitle><description>Background: The aim of the present study was to explore risk variants for coronary artery disease (CAD) and to evaluate their joint effects (quantified by genetic risk score; GRS) on the discrimination of CAD in a Chinese Han sample. Methods and Results: An association analysis of 91 single nucleotide polymorphisms (SNPs) with CAD risk was undertaken in 1,007 CAD patients and 889 healthy controls. Two GRSs, counted GRS (cGRS) and weighted GRS (wGRS), were calculated using the significant SNPs, and their discriminant power for CAD was assessed using receiver-operating characteristic (ROC) curve analysis. Eight SNPs (rs11206510, rs10118757, rs2383206, rs501120, rs2075292, rs174547, rs173539, and rs255052) were nominally significantly associated with CAD (P&lt;0.05), and 5 of them were newly reported. The GRSs derived from the 8 SNPs improved the discrimination of CAD compared to that using 4 conventional risk factors (P=0.002 for cGRS and P=0.009 for wGRS). After 10-fold cross-validation 100 times, the average areas under the curve were 0.668 (95% confidence interval [CI]: 0.667-0.669), 0.686 (95% CI: 0.685-0.687) and 0.690 (95% CI: 0.689-0.691) for models with conventional risk factors only, conventional risk factors plus cGRS, and conventional risk factors plus wGRS, respectively. Conclusions: A multigenic GRS, generated by combining multiple gene variants, can improve discrimination of CAD, thereby confirming the joint effects of these gene variants on CAD in this Chinese Han population.  (Circ J 2012; 76: 1987–1992)</description><subject>Aged</subject><subject>Asian Continental Ancestry Group</subject><subject>China - epidemiology</subject><subject>Coronary artery disease</subject><subject>Coronary Artery Disease - epidemiology</subject><subject>Coronary Artery Disease - genetics</subject><subject>Female</subject><subject>Genetic Loci</subject><subject>Genetic risk score</subject><subject>Genetic variants</subject><subject>Humans</subject><subject>Joint effect</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multifactorial Inheritance</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Risk Factors</subject><subject>ROC Curve</subject><issn>1346-9843</issn><issn>1347-4820</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkDtv7CAQhVF0o7z7VFeUt3EC2MamjJznaqNIebUI4_FdNl7YAC7y74Ozm6RhhtF3zmgOQqeUnFFW5ufaeL08a2YZZRmhJd9BBzQvqqyoGfnz1fNM1EW-jw5DWBLCBCnFHtpnjPOCF-QAvc-csRFf9T3oGLDr8Q1YiEbjV-WNsmlmLL4fh2jWA-C50wY7i-MC8KMJb5Ogcd5Z5T_whY-QyqUJoAJMumZhLKT2Vln8NLbLaccx2u3VEOBkW4_Qy_XVc3ObzR9u7pqLeaZLUcYMelprmled0CXhHetrLXjfUsIr0hWCC0o7nm4mtFO0pTmteVWyTjBWtipPgyP0b-O79u59hBDlygQNw6AsuDFISnJSVwWtioSSDaq9C8FDL9ferNJJCZJT0PIraNnM0k9OQSfJ36372K6g-xF8J5uA6w2wDFH9hx9A-RTuAFvHist6en6df4GF8hJs_gl_NJJ6</recordid><startdate>2012</startdate><enddate>2012</enddate><creator>Lv, Xiaofei</creator><creator>Zhang, Yuan</creator><creator>Rao, Shaoqi</creator><creator>Qiu, Jian</creator><creator>Wang, Min</creator><creator>Luo, Xiaoqin</creator><creator>Zuo, Xiaoyu</creator><creator>Su, Dongfang</creator><creator>Feng, Xiang</creator><creator>Yang, Yan</creator><creator>Ouyang, Ping</creator><creator>Chen, Yibing</creator><creator>Li, Xinrui</creator><creator>Xiao, Yunjun</creator><creator>Ling, Wenhua</creator><general>The Japanese Circulation Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>2012</creationdate><title>Joint Effects of Genetic Variants in Multiple Loci on the Risk of Coronary Artery Disease in Chinese Han Subjects</title><author>Lv, Xiaofei ; Zhang, Yuan ; Rao, Shaoqi ; Qiu, Jian ; Wang, Min ; Luo, Xiaoqin ; Zuo, Xiaoyu ; Su, Dongfang ; Feng, Xiang ; Yang, Yan ; Ouyang, Ping ; Chen, Yibing ; Li, Xinrui ; Xiao, Yunjun ; Ling, Wenhua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c595t-ef18c137d9c506d2f8c96fb10670d496911d601501da1b13186752d9225ba3b13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Aged</topic><topic>Asian Continental Ancestry Group</topic><topic>China - epidemiology</topic><topic>Coronary artery disease</topic><topic>Coronary Artery Disease - epidemiology</topic><topic>Coronary Artery Disease - genetics</topic><topic>Female</topic><topic>Genetic Loci</topic><topic>Genetic risk score</topic><topic>Genetic variants</topic><topic>Humans</topic><topic>Joint effect</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Multifactorial Inheritance</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Risk Factors</topic><topic>ROC Curve</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lv, Xiaofei</creatorcontrib><creatorcontrib>Zhang, Yuan</creatorcontrib><creatorcontrib>Rao, Shaoqi</creatorcontrib><creatorcontrib>Qiu, Jian</creatorcontrib><creatorcontrib>Wang, Min</creatorcontrib><creatorcontrib>Luo, Xiaoqin</creatorcontrib><creatorcontrib>Zuo, Xiaoyu</creatorcontrib><creatorcontrib>Su, Dongfang</creatorcontrib><creatorcontrib>Feng, Xiang</creatorcontrib><creatorcontrib>Yang, Yan</creatorcontrib><creatorcontrib>Ouyang, Ping</creatorcontrib><creatorcontrib>Chen, Yibing</creatorcontrib><creatorcontrib>Li, Xinrui</creatorcontrib><creatorcontrib>Xiao, Yunjun</creatorcontrib><creatorcontrib>Ling, Wenhua</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation Journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lv, Xiaofei</au><au>Zhang, Yuan</au><au>Rao, Shaoqi</au><au>Qiu, Jian</au><au>Wang, Min</au><au>Luo, Xiaoqin</au><au>Zuo, Xiaoyu</au><au>Su, Dongfang</au><au>Feng, Xiang</au><au>Yang, Yan</au><au>Ouyang, Ping</au><au>Chen, Yibing</au><au>Li, Xinrui</au><au>Xiao, Yunjun</au><au>Ling, Wenhua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Joint Effects of Genetic Variants in Multiple Loci on the Risk of Coronary Artery Disease in Chinese Han Subjects</atitle><jtitle>Circulation Journal</jtitle><addtitle>Circ J</addtitle><date>2012</date><risdate>2012</risdate><volume>76</volume><issue>8</issue><spage>1987</spage><epage>1992</epage><pages>1987-1992</pages><issn>1346-9843</issn><eissn>1347-4820</eissn><abstract>Background: The aim of the present study was to explore risk variants for coronary artery disease (CAD) and to evaluate their joint effects (quantified by genetic risk score; GRS) on the discrimination of CAD in a Chinese Han sample. Methods and Results: An association analysis of 91 single nucleotide polymorphisms (SNPs) with CAD risk was undertaken in 1,007 CAD patients and 889 healthy controls. Two GRSs, counted GRS (cGRS) and weighted GRS (wGRS), were calculated using the significant SNPs, and their discriminant power for CAD was assessed using receiver-operating characteristic (ROC) curve analysis. Eight SNPs (rs11206510, rs10118757, rs2383206, rs501120, rs2075292, rs174547, rs173539, and rs255052) were nominally significantly associated with CAD (P&lt;0.05), and 5 of them were newly reported. The GRSs derived from the 8 SNPs improved the discrimination of CAD compared to that using 4 conventional risk factors (P=0.002 for cGRS and P=0.009 for wGRS). After 10-fold cross-validation 100 times, the average areas under the curve were 0.668 (95% confidence interval [CI]: 0.667-0.669), 0.686 (95% CI: 0.685-0.687) and 0.690 (95% CI: 0.689-0.691) for models with conventional risk factors only, conventional risk factors plus cGRS, and conventional risk factors plus wGRS, respectively. Conclusions: A multigenic GRS, generated by combining multiple gene variants, can improve discrimination of CAD, thereby confirming the joint effects of these gene variants on CAD in this Chinese Han population.  (Circ J 2012; 76: 1987–1992)</abstract><cop>Japan</cop><pub>The Japanese Circulation Society</pub><pmid>22664640</pmid><doi>10.1253/circj.CJ-12-0156</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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subjects Aged
Asian Continental Ancestry Group
China - epidemiology
Coronary artery disease
Coronary Artery Disease - epidemiology
Coronary Artery Disease - genetics
Female
Genetic Loci
Genetic risk score
Genetic variants
Humans
Joint effect
Male
Middle Aged
Multifactorial Inheritance
Polymorphism, Single Nucleotide
Risk Factors
ROC Curve
title Joint Effects of Genetic Variants in Multiple Loci on the Risk of Coronary Artery Disease in Chinese Han Subjects
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