A genome-wide association study reveals susceptibility loci for myocardial infarction/coronary artery disease in Saudi Arabs
Abstract Background Multiple loci have been identified for coronary artery disease (CAD) by genome-wide association studies (GWAS), but no such studies on CAD incidence has been reported yet for any Middle Eastern population. Methods In this study, we performed a GWAS for CAD and myocardial infarcti...
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| Veröffentlicht in: | Atherosclerosis 2016-02, Vol.245, p.62-70 |
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| creator | Wakil, Salma M Ram, Ramesh Muiya, Nzioka P Mehta, Munish Andres, Editha Mazhar, Nejat Baz, Batoul Hagos, Samya Alshahid, Maie Meyer, Brian F Morahan, Grant Dzimiri, Nduna |
| description | Abstract Background Multiple loci have been identified for coronary artery disease (CAD) by genome-wide association studies (GWAS), but no such studies on CAD incidence has been reported yet for any Middle Eastern population. Methods In this study, we performed a GWAS for CAD and myocardial infarction (MI) incidence in 5668 Saudis of Arab descent using the Affymetrix Axiom Genotyping platform. Results We describe SNPs at 16 loci that showed significant (P |
| doi_str_mv | 10.1016/j.atherosclerosis.2015.11.019 |
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| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1762026396</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S002191501530215X</els_id><sourcerecordid>1762026396</sourcerecordid><originalsourceid>FETCH-LOGICAL-c444t-e542b879847ed5aa1bbf05bff5f1d7bad8e1956dec07a4fd942c983bcdc6b0193</originalsourceid><addsrcrecordid>eNqNUk1v1DAUtBCIbgt_AfmCxCWpX2Ln4wDSqoIWqRKHgsTN8sczeEnixU6KIvHjcbSFQ09c_HyYN6OZeYS8BlYCg-byUKr5O8aQzLC9PpUVA1EClAz6J2QHXdsXwDv-lOwYq6DoQbAzcp7SgTHGW-iek7OqaVlXdWJHfu_pN5zCiMUvb5GqlILxavZhomle7Eoj3qMaEk1LMnicvfaDn1c6ZBh1IdJxDUZF69VA_eRUNNvupQkxTCquVMUZ87A-oUqYIfROLdbTfVQ6vSDPXObGlw_zgnz58P7z1U1x--n649X-tjCc87lAwSudbXW8RSuUAq0dE9o54cC2WtkOoReNRcNaxZ3teWX6rtbGmkbnVOoL8ubEe4zh54JplqPPboZBTRiWJKFtKlY1dd9k6NsT1ORwU0Qnj9GP2YkEJrcC5EE-KkBuBUgAeZJ69SC16BHtv-2_iWfA9QmA2fC9xyiT8TgZtD6imaUN_r-l3j1iMoOfvFHDD1wxHcISp5yqBJkqyeTddg3bMYCo8098rf8AmLy6IQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1762026396</pqid></control><display><type>article</type><title>A genome-wide association study reveals susceptibility loci for myocardial infarction/coronary artery disease in Saudi Arabs</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Wakil, Salma M ; Ram, Ramesh ; Muiya, Nzioka P ; Mehta, Munish ; Andres, Editha ; Mazhar, Nejat ; Baz, Batoul ; Hagos, Samya ; Alshahid, Maie ; Meyer, Brian F ; Morahan, Grant ; Dzimiri, Nduna</creator><creatorcontrib>Wakil, Salma M ; Ram, Ramesh ; Muiya, Nzioka P ; Mehta, Munish ; Andres, Editha ; Mazhar, Nejat ; Baz, Batoul ; Hagos, Samya ; Alshahid, Maie ; Meyer, Brian F ; Morahan, Grant ; Dzimiri, Nduna</creatorcontrib><description>Abstract Background Multiple loci have been identified for coronary artery disease (CAD) by genome-wide association studies (GWAS), but no such studies on CAD incidence has been reported yet for any Middle Eastern population. Methods In this study, we performed a GWAS for CAD and myocardial infarction (MI) incidence in 5668 Saudis of Arab descent using the Affymetrix Axiom Genotyping platform. Results We describe SNPs at 16 loci that showed significant (P < 5 × 10−8 ) or suggestive GWAS association (P < 1 × 10−5 ) with CAD or MI, in the ethnic Saudi Arab population. Among the four variants reaching GWAS significance in the present study, the rs10738607_G [0.78(0.71–0.85); p = 2.17E-08] in CDNK2A/B gene was associated with CAD. Two other SNPs on the same gene, rs10757274_G [0.79(0.73–0.86); p = 2.98E-08] and rs1333045_C [0.79(0.73–0.86); p = 1.15E-08] as well as the rs9982601_T [1.38(1.23–1.55); p = 3.49E-08] on KCNE2 were associated with MI. These variants have been previously described in other populations. Several SNPs, including the rs7421388 ( PLCL1) and rs12541758 ( TRPA1) displaying a suggestive GWAS association (P < 1 × 10−5 ) with CAD as well as rs41411047 ( RNF13 ), rs32793 ( PDZD2 ) and rs4739066 ( YTHDF3 ), similarly showing weak association with MI, were confirmed in an independent dataset. Furthermore, our estimation of heritability of CAD and MI based on observed genome-wide sharing in unrelated Saudi Arabs was approximately 33% and 44%, respectively. Conclusions Our study has identified susceptibility variants for CAD/MI in ethnic Arabs. These findings provide further insights into pathways contributing to the susceptibility for CAD and will enable more comprehensive genetic studies of these diseases in Middle East populations.</description><identifier>ISSN: 0021-9150</identifier><identifier>EISSN: 1879-1484</identifier><identifier>DOI: 10.1016/j.atherosclerosis.2015.11.019</identifier><identifier>PMID: 26708285</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Cardiovascular ; CDKN2A/B ; Coronary artery disease ; Coronary Artery Disease - genetics ; Coronary Artery Disease - metabolism ; CXCL12 ; Female ; Genetic Predisposition to Disease ; Genome-wide association ; Genome-Wide Association Study - methods ; Genotype ; Haplotypes ; Heritability ; Humans ; Incidence ; KCNE2 ; Male ; Middle Aged ; Myocardial infarction ; Myocardial Infarction - epidemiology ; Myocardial Infarction - genetics ; Myocardial Infarction - metabolism ; Risk Factors ; Saudi Arabia - epidemiology</subject><ispartof>Atherosclerosis, 2016-02, Vol.245, p.62-70</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2015 Elsevier Ireland Ltd</rights><rights>Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c444t-e542b879847ed5aa1bbf05bff5f1d7bad8e1956dec07a4fd942c983bcdc6b0193</citedby><cites>FETCH-LOGICAL-c444t-e542b879847ed5aa1bbf05bff5f1d7bad8e1956dec07a4fd942c983bcdc6b0193</cites><orcidid>0000-0003-3395-5754 ; 0000-0003-0135-4946</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S002191501530215X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26708285$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wakil, Salma M</creatorcontrib><creatorcontrib>Ram, Ramesh</creatorcontrib><creatorcontrib>Muiya, Nzioka P</creatorcontrib><creatorcontrib>Mehta, Munish</creatorcontrib><creatorcontrib>Andres, Editha</creatorcontrib><creatorcontrib>Mazhar, Nejat</creatorcontrib><creatorcontrib>Baz, Batoul</creatorcontrib><creatorcontrib>Hagos, Samya</creatorcontrib><creatorcontrib>Alshahid, Maie</creatorcontrib><creatorcontrib>Meyer, Brian F</creatorcontrib><creatorcontrib>Morahan, Grant</creatorcontrib><creatorcontrib>Dzimiri, Nduna</creatorcontrib><title>A genome-wide association study reveals susceptibility loci for myocardial infarction/coronary artery disease in Saudi Arabs</title><title>Atherosclerosis</title><addtitle>Atherosclerosis</addtitle><description>Abstract Background Multiple loci have been identified for coronary artery disease (CAD) by genome-wide association studies (GWAS), but no such studies on CAD incidence has been reported yet for any Middle Eastern population. Methods In this study, we performed a GWAS for CAD and myocardial infarction (MI) incidence in 5668 Saudis of Arab descent using the Affymetrix Axiom Genotyping platform. Results We describe SNPs at 16 loci that showed significant (P < 5 × 10−8 ) or suggestive GWAS association (P < 1 × 10−5 ) with CAD or MI, in the ethnic Saudi Arab population. Among the four variants reaching GWAS significance in the present study, the rs10738607_G [0.78(0.71–0.85); p = 2.17E-08] in CDNK2A/B gene was associated with CAD. Two other SNPs on the same gene, rs10757274_G [0.79(0.73–0.86); p = 2.98E-08] and rs1333045_C [0.79(0.73–0.86); p = 1.15E-08] as well as the rs9982601_T [1.38(1.23–1.55); p = 3.49E-08] on KCNE2 were associated with MI. These variants have been previously described in other populations. Several SNPs, including the rs7421388 ( PLCL1) and rs12541758 ( TRPA1) displaying a suggestive GWAS association (P < 1 × 10−5 ) with CAD as well as rs41411047 ( RNF13 ), rs32793 ( PDZD2 ) and rs4739066 ( YTHDF3 ), similarly showing weak association with MI, were confirmed in an independent dataset. Furthermore, our estimation of heritability of CAD and MI based on observed genome-wide sharing in unrelated Saudi Arabs was approximately 33% and 44%, respectively. Conclusions Our study has identified susceptibility variants for CAD/MI in ethnic Arabs. These findings provide further insights into pathways contributing to the susceptibility for CAD and will enable more comprehensive genetic studies of these diseases in Middle East populations.</description><subject>Cardiovascular</subject><subject>CDKN2A/B</subject><subject>Coronary artery disease</subject><subject>Coronary Artery Disease - genetics</subject><subject>Coronary Artery Disease - metabolism</subject><subject>CXCL12</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>Genome-wide association</subject><subject>Genome-Wide Association Study - methods</subject><subject>Genotype</subject><subject>Haplotypes</subject><subject>Heritability</subject><subject>Humans</subject><subject>Incidence</subject><subject>KCNE2</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Myocardial infarction</subject><subject>Myocardial Infarction - epidemiology</subject><subject>Myocardial Infarction - genetics</subject><subject>Myocardial Infarction - metabolism</subject><subject>Risk Factors</subject><subject>Saudi Arabia - epidemiology</subject><issn>0021-9150</issn><issn>1879-1484</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUk1v1DAUtBCIbgt_AfmCxCWpX2Ln4wDSqoIWqRKHgsTN8sczeEnixU6KIvHjcbSFQ09c_HyYN6OZeYS8BlYCg-byUKr5O8aQzLC9PpUVA1EClAz6J2QHXdsXwDv-lOwYq6DoQbAzcp7SgTHGW-iek7OqaVlXdWJHfu_pN5zCiMUvb5GqlILxavZhomle7Eoj3qMaEk1LMnicvfaDn1c6ZBh1IdJxDUZF69VA_eRUNNvupQkxTCquVMUZ87A-oUqYIfROLdbTfVQ6vSDPXObGlw_zgnz58P7z1U1x--n649X-tjCc87lAwSudbXW8RSuUAq0dE9o54cC2WtkOoReNRcNaxZ3teWX6rtbGmkbnVOoL8ubEe4zh54JplqPPboZBTRiWJKFtKlY1dd9k6NsT1ORwU0Qnj9GP2YkEJrcC5EE-KkBuBUgAeZJ69SC16BHtv-2_iWfA9QmA2fC9xyiT8TgZtD6imaUN_r-l3j1iMoOfvFHDD1wxHcISp5yqBJkqyeTddg3bMYCo8098rf8AmLy6IQ</recordid><startdate>20160201</startdate><enddate>20160201</enddate><creator>Wakil, Salma M</creator><creator>Ram, Ramesh</creator><creator>Muiya, Nzioka P</creator><creator>Mehta, Munish</creator><creator>Andres, Editha</creator><creator>Mazhar, Nejat</creator><creator>Baz, Batoul</creator><creator>Hagos, Samya</creator><creator>Alshahid, Maie</creator><creator>Meyer, Brian F</creator><creator>Morahan, Grant</creator><creator>Dzimiri, Nduna</creator><general>Elsevier B.V</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><orcidid>https://orcid.org/0000-0003-3395-5754</orcidid><orcidid>https://orcid.org/0000-0003-0135-4946</orcidid></search><sort><creationdate>20160201</creationdate><title>A genome-wide association study reveals susceptibility loci for myocardial infarction/coronary artery disease in Saudi Arabs</title><author>Wakil, Salma M ; Ram, Ramesh ; Muiya, Nzioka P ; Mehta, Munish ; Andres, Editha ; Mazhar, Nejat ; Baz, Batoul ; Hagos, Samya ; Alshahid, Maie ; Meyer, Brian F ; Morahan, Grant ; Dzimiri, Nduna</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c444t-e542b879847ed5aa1bbf05bff5f1d7bad8e1956dec07a4fd942c983bcdc6b0193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Cardiovascular</topic><topic>CDKN2A/B</topic><topic>Coronary artery disease</topic><topic>Coronary Artery Disease - genetics</topic><topic>Coronary Artery Disease - metabolism</topic><topic>CXCL12</topic><topic>Female</topic><topic>Genetic Predisposition to Disease</topic><topic>Genome-wide association</topic><topic>Genome-Wide Association Study - methods</topic><topic>Genotype</topic><topic>Haplotypes</topic><topic>Heritability</topic><topic>Humans</topic><topic>Incidence</topic><topic>KCNE2</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Myocardial infarction</topic><topic>Myocardial Infarction - epidemiology</topic><topic>Myocardial Infarction - genetics</topic><topic>Myocardial Infarction - metabolism</topic><topic>Risk Factors</topic><topic>Saudi Arabia - epidemiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wakil, Salma M</creatorcontrib><creatorcontrib>Ram, Ramesh</creatorcontrib><creatorcontrib>Muiya, Nzioka P</creatorcontrib><creatorcontrib>Mehta, Munish</creatorcontrib><creatorcontrib>Andres, Editha</creatorcontrib><creatorcontrib>Mazhar, Nejat</creatorcontrib><creatorcontrib>Baz, Batoul</creatorcontrib><creatorcontrib>Hagos, Samya</creatorcontrib><creatorcontrib>Alshahid, Maie</creatorcontrib><creatorcontrib>Meyer, Brian F</creatorcontrib><creatorcontrib>Morahan, Grant</creatorcontrib><creatorcontrib>Dzimiri, Nduna</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>Atherosclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wakil, Salma M</au><au>Ram, Ramesh</au><au>Muiya, Nzioka P</au><au>Mehta, Munish</au><au>Andres, Editha</au><au>Mazhar, Nejat</au><au>Baz, Batoul</au><au>Hagos, Samya</au><au>Alshahid, Maie</au><au>Meyer, Brian F</au><au>Morahan, Grant</au><au>Dzimiri, Nduna</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A genome-wide association study reveals susceptibility loci for myocardial infarction/coronary artery disease in Saudi Arabs</atitle><jtitle>Atherosclerosis</jtitle><addtitle>Atherosclerosis</addtitle><date>2016-02-01</date><risdate>2016</risdate><volume>245</volume><spage>62</spage><epage>70</epage><pages>62-70</pages><issn>0021-9150</issn><eissn>1879-1484</eissn><abstract>Abstract Background Multiple loci have been identified for coronary artery disease (CAD) by genome-wide association studies (GWAS), but no such studies on CAD incidence has been reported yet for any Middle Eastern population. Methods In this study, we performed a GWAS for CAD and myocardial infarction (MI) incidence in 5668 Saudis of Arab descent using the Affymetrix Axiom Genotyping platform. Results We describe SNPs at 16 loci that showed significant (P < 5 × 10−8 ) or suggestive GWAS association (P < 1 × 10−5 ) with CAD or MI, in the ethnic Saudi Arab population. Among the four variants reaching GWAS significance in the present study, the rs10738607_G [0.78(0.71–0.85); p = 2.17E-08] in CDNK2A/B gene was associated with CAD. Two other SNPs on the same gene, rs10757274_G [0.79(0.73–0.86); p = 2.98E-08] and rs1333045_C [0.79(0.73–0.86); p = 1.15E-08] as well as the rs9982601_T [1.38(1.23–1.55); p = 3.49E-08] on KCNE2 were associated with MI. These variants have been previously described in other populations. Several SNPs, including the rs7421388 ( PLCL1) and rs12541758 ( TRPA1) displaying a suggestive GWAS association (P < 1 × 10−5 ) with CAD as well as rs41411047 ( RNF13 ), rs32793 ( PDZD2 ) and rs4739066 ( YTHDF3 ), similarly showing weak association with MI, were confirmed in an independent dataset. Furthermore, our estimation of heritability of CAD and MI based on observed genome-wide sharing in unrelated Saudi Arabs was approximately 33% and 44%, respectively. Conclusions Our study has identified susceptibility variants for CAD/MI in ethnic Arabs. These findings provide further insights into pathways contributing to the susceptibility for CAD and will enable more comprehensive genetic studies of these diseases in Middle East populations.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>26708285</pmid><doi>10.1016/j.atherosclerosis.2015.11.019</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-3395-5754</orcidid><orcidid>https://orcid.org/0000-0003-0135-4946</orcidid></addata></record> |
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| subjects | Cardiovascular CDKN2A/B Coronary artery disease Coronary Artery Disease - genetics Coronary Artery Disease - metabolism CXCL12 Female Genetic Predisposition to Disease Genome-wide association Genome-Wide Association Study - methods Genotype Haplotypes Heritability Humans Incidence KCNE2 Male Middle Aged Myocardial infarction Myocardial Infarction - epidemiology Myocardial Infarction - genetics Myocardial Infarction - metabolism Risk Factors Saudi Arabia - epidemiology |
| title | A genome-wide association study reveals susceptibility loci for myocardial infarction/coronary artery disease in Saudi Arabs |
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