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Uncovering myocardial infarction genetic signatures using GWAS exploration in Saudi and European cohorts
Genome-wide association studies (GWAS) have yielded significant insights into the genetic architecture of myocardial infarction (MI), although studies in non-European populations are still lacking. Saudi Arabian cohorts offer an opportunity to discover novel genetic variants impacting disease risk d...
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| Published in: | Scientific reports 2023-12, Vol.13 (1), p.21866-21866, Article 21866 |
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| creator | Al-Ali, Amein K. Al-Rubaish, Abdullah M. Alali, Rudaynah A. Almansori, Mohammed S. Al-Jumaan, Mohammed A. Alshehri, Abdullah M. Al-Madan, Mohammed S. Vatte, ChittiBabu Cherlin, Tess Young, Sylvia Verma, Shefali S. Morahan, Grant Koeleman, Bobby P. C. Keating, Brendan J. |
| description | Genome-wide association studies (GWAS) have yielded significant insights into the genetic architecture of myocardial infarction (MI), although studies in non-European populations are still lacking. Saudi Arabian cohorts offer an opportunity to discover novel genetic variants impacting disease risk due to a high rate of consanguinity. Genome-wide genotyping (GWG), imputation and GWAS followed by meta-analysis were performed based on two independent Saudi Arabian studies comprising 3950 MI patients and 2324 non-MI controls. Meta-analyses were then performed with these two Saudi MI studies and the CardioGRAMplusC4D and UK BioBank GWAS as controls. Meta-analyses of the two Saudi MI studies resulted in 17 SNPs with genome-wide significance. Meta-analyses of all 4 studies revealed 66 loci with genome-wide significance levels of p 12% MAF). In conclusion, our results replicated many MI associations, whereas in Saudi-only GWAS (meta-analyses), several new loci were implicated that require future validation and functional analyses. |
| doi_str_mv | 10.1038/s41598-023-49105-1 |
| format | article |
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–8
. All of these variants, except
rs2764203
, have previously been reported as MI-associated loci or to have high linkage disequilibrium with known loci. One SNP association in
Shisa family member 5
(
SHISA5
) (rs11707229) was evident at a much higher frequency in the Saudi MI populations (> 12% MAF). In conclusion, our results replicated many MI associations, whereas in Saudi-only GWAS (meta-analyses), several new loci were implicated that require future validation and functional analyses.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-023-49105-1</identifier><identifier>PMID: 38072966</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/208 ; 631/45 ; 692/4019 ; Consanguinity ; Genetic diversity ; Genetic Predisposition to Disease ; Genetic variance ; Genome-wide association studies ; Genome-Wide Association Study - methods ; Genomes ; Genotype ; Genotyping ; Health risks ; Heart attacks ; Humanities and Social Sciences ; Humans ; Linkage disequilibrium ; Meta-analysis ; multidisciplinary ; Myocardial infarction ; Myocardial Infarction - genetics ; Polymorphism, Single Nucleotide ; Population studies ; Saudi Arabia ; Science ; Science (multidisciplinary) ; Single-nucleotide polymorphism</subject><ispartof>Scientific reports, 2023-12, Vol.13 (1), p.21866-21866, Article 21866</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c492t-b775ab9e1c5affe5215fe528432c9a86b369de9e49dcd3cfa708881098d12f623</cites><orcidid>0000-0002-0673-3534</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2900125468/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2900125468?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25752,27923,27924,37011,37012,44589,53790,53792,74897</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38072966$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Al-Ali, Amein K.</creatorcontrib><creatorcontrib>Al-Rubaish, Abdullah M.</creatorcontrib><creatorcontrib>Alali, Rudaynah A.</creatorcontrib><creatorcontrib>Almansori, Mohammed S.</creatorcontrib><creatorcontrib>Al-Jumaan, Mohammed A.</creatorcontrib><creatorcontrib>Alshehri, Abdullah M.</creatorcontrib><creatorcontrib>Al-Madan, Mohammed S.</creatorcontrib><creatorcontrib>Vatte, ChittiBabu</creatorcontrib><creatorcontrib>Cherlin, Tess</creatorcontrib><creatorcontrib>Young, Sylvia</creatorcontrib><creatorcontrib>Verma, Shefali S.</creatorcontrib><creatorcontrib>Morahan, Grant</creatorcontrib><creatorcontrib>Koeleman, Bobby P. C.</creatorcontrib><creatorcontrib>Keating, Brendan J.</creatorcontrib><title>Uncovering myocardial infarction genetic signatures using GWAS exploration in Saudi and European cohorts</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Genome-wide association studies (GWAS) have yielded significant insights into the genetic architecture of myocardial infarction (MI), although studies in non-European populations are still lacking. Saudi Arabian cohorts offer an opportunity to discover novel genetic variants impacting disease risk due to a high rate of consanguinity. Genome-wide genotyping (GWG), imputation and GWAS followed by meta-analysis were performed based on two independent Saudi Arabian studies comprising 3950 MI patients and 2324 non-MI controls. Meta-analyses were then performed with these two Saudi MI studies and the CardioGRAMplusC4D and UK BioBank GWAS as controls. Meta-analyses of the two Saudi MI studies resulted in 17 SNPs with genome-wide significance. Meta-analyses of all 4 studies revealed 66 loci with genome-wide significance levels of p < 5 × 10
–8
. All of these variants, except
rs2764203
, have previously been reported as MI-associated loci or to have high linkage disequilibrium with known loci. One SNP association in
Shisa family member 5
(
SHISA5
) (rs11707229) was evident at a much higher frequency in the Saudi MI populations (> 12% MAF). In conclusion, our results replicated many MI associations, whereas in Saudi-only GWAS (meta-analyses), several new loci were implicated that require future validation and functional analyses.</description><subject>631/208</subject><subject>631/45</subject><subject>692/4019</subject><subject>Consanguinity</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic variance</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study - methods</subject><subject>Genomes</subject><subject>Genotype</subject><subject>Genotyping</subject><subject>Health risks</subject><subject>Heart attacks</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Linkage disequilibrium</subject><subject>Meta-analysis</subject><subject>multidisciplinary</subject><subject>Myocardial infarction</subject><subject>Myocardial Infarction - genetics</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population studies</subject><subject>Saudi Arabia</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Single-nucleotide polymorphism</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp9ks1u1DAURiMEolXpC7BAltiwCfg3sVeoqkqpVIlFqVhaN85NxqOMHeykom9PMlNKywIvbMs-Pte2vqJ4y-hHRoX-lCVTRpeUi1IaRlXJXhTHnEpVcsH5yyfzo-I05y1dmuJGMvO6OBKa1txU1XGxuQ0u3mHyoSe7--ggtR4G4kMHyU0-BtJjwMk7kn0fYJoTZjLnFb_8cXZD8Nc4xAR70gdyA3PrCYSWXMwpjgiBuLiJacpvilcdDBlPH8aT4vbLxffzr-X1t8ur87Pr0knDp7KpawWNQeYUdB0qztTaaym4M6CrRlSmRYPStK4VroOaaq0ZNbplvKu4OCmuDt42wtaOye8g3dsI3u4XYuotpOU9A1pQSsuGMlRVLWux6CkFYJWmGlBUbHF9PrjGudlh6zBMCYZn0uc7wW9sH-8sozVjlNPF8OHBkOLPGfNkdz47HAYIGOdsuaHciNrQtdj7f9BtnFNY_mqlKONKVnqh-IFyKeacsHu8DaN2DYY9BMMuwbD7YNhV_e7pOx6P_InBAogDkMc1CZj-1v6P9jfpCsQR</recordid><startdate>20231210</startdate><enddate>20231210</enddate><creator>Al-Ali, Amein K.</creator><creator>Al-Rubaish, Abdullah M.</creator><creator>Alali, Rudaynah A.</creator><creator>Almansori, Mohammed S.</creator><creator>Al-Jumaan, Mohammed A.</creator><creator>Alshehri, Abdullah M.</creator><creator>Al-Madan, Mohammed S.</creator><creator>Vatte, ChittiBabu</creator><creator>Cherlin, Tess</creator><creator>Young, Sylvia</creator><creator>Verma, Shefali S.</creator><creator>Morahan, Grant</creator><creator>Koeleman, Bobby P. 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C.</au><au>Keating, Brendan J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Uncovering myocardial infarction genetic signatures using GWAS exploration in Saudi and European cohorts</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2023-12-10</date><risdate>2023</risdate><volume>13</volume><issue>1</issue><spage>21866</spage><epage>21866</epage><pages>21866-21866</pages><artnum>21866</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Genome-wide association studies (GWAS) have yielded significant insights into the genetic architecture of myocardial infarction (MI), although studies in non-European populations are still lacking. Saudi Arabian cohorts offer an opportunity to discover novel genetic variants impacting disease risk due to a high rate of consanguinity. Genome-wide genotyping (GWG), imputation and GWAS followed by meta-analysis were performed based on two independent Saudi Arabian studies comprising 3950 MI patients and 2324 non-MI controls. Meta-analyses were then performed with these two Saudi MI studies and the CardioGRAMplusC4D and UK BioBank GWAS as controls. Meta-analyses of the two Saudi MI studies resulted in 17 SNPs with genome-wide significance. Meta-analyses of all 4 studies revealed 66 loci with genome-wide significance levels of p < 5 × 10
–8
. All of these variants, except
rs2764203
, have previously been reported as MI-associated loci or to have high linkage disequilibrium with known loci. One SNP association in
Shisa family member 5
(
SHISA5
) (rs11707229) was evident at a much higher frequency in the Saudi MI populations (> 12% MAF). In conclusion, our results replicated many MI associations, whereas in Saudi-only GWAS (meta-analyses), several new loci were implicated that require future validation and functional analyses.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>38072966</pmid><doi>10.1038/s41598-023-49105-1</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-0673-3534</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Publicly Available Content Database; Full-Text Journals in Chemistry (Open access); PubMed Central; Springer Nature - nature.com Journals - Fully Open Access |
| subjects | 631/208 631/45 692/4019 Consanguinity Genetic diversity Genetic Predisposition to Disease Genetic variance Genome-wide association studies Genome-Wide Association Study - methods Genomes Genotype Genotyping Health risks Heart attacks Humanities and Social Sciences Humans Linkage disequilibrium Meta-analysis multidisciplinary Myocardial infarction Myocardial Infarction - genetics Polymorphism, Single Nucleotide Population studies Saudi Arabia Science Science (multidisciplinary) Single-nucleotide polymorphism |
| title | Uncovering myocardial infarction genetic signatures using GWAS exploration in Saudi and European cohorts |
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