Uncovering myocardial infarction genetic signatures using GWAS exploration in Saudi and European cohorts
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 disea...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-12-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-49105-1 |
| _version_ | 1797398029812105216 |
|---|---|
| author | Amein K. Al-Ali Abdullah M. Al-Rubaish Rudaynah A. Alali Mohammed S. Almansori Mohammed A. Al-Jumaan Abdullah M. Alshehri Mohammed S. Al-Madan ChittiBabu Vatte Tess Cherlin Sylvia Young Shefali S. Verma Grant Morahan Bobby P. C. Koeleman Brendan J. Keating |
| author_facet | Amein K. Al-Ali Abdullah M. Al-Rubaish Rudaynah A. Alali Mohammed S. Almansori Mohammed A. Al-Jumaan Abdullah M. Alshehri Mohammed S. Al-Madan ChittiBabu Vatte Tess Cherlin Sylvia Young Shefali S. Verma Grant Morahan Bobby P. C. Koeleman Brendan J. Keating |
| author_sort | Amein K. Al-Ali |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T01:19:45Z |
| format | Article |
| id | doaj.art-a5584b01e5674739a800aa16808ae361 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T01:19:45Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a5584b01e5674739a800aa16808ae3612023-12-10T12:14:57ZengNature PortfolioScientific Reports2045-23222023-12-0113111010.1038/s41598-023-49105-1Uncovering myocardial infarction genetic signatures using GWAS exploration in Saudi and European cohortsAmein K. Al-Ali0Abdullah M. Al-Rubaish1Rudaynah A. Alali2Mohammed S. Almansori3Mohammed A. Al-Jumaan4Abdullah M. Alshehri5Mohammed S. Al-Madan6ChittiBabu Vatte7Tess Cherlin8Sylvia Young9Shefali S. Verma10Grant Morahan11Bobby P. C. Koeleman12Brendan J. Keating13Department of Clinical Biochemistry, College of Medicine, Imam Abdulrahman bin Faisal UniversityDepartment of Internal Medicine, King Fahd Hospital of the UniversityDepartment of Internal Medicine, King Fahd Hospital of the UniversityDepartment of Internal Medicine, King Fahd Hospital of the UniversityCollege of Medicine, Imam Abdulrahman bin Faisal UniversityDepartment of Internal Medicine, King Fahd Hospital of the UniversityCollege of Medicine, Imam Abdulrahman bin Faisal UniversityDepartment of Clinical Biochemistry, College of Medicine, Imam Abdulrahman bin Faisal UniversityDepartment of Pathology and Laboratory Medicine, University of PennsylvaniaCentre for Diabetes Research, Harry Perkins Institute of Medical Research, University of Western AustraliaDepartment of Pathology and Laboratory Medicine, University of PennsylvaniaCentre for Diabetes Research, Harry Perkins Institute of Medical Research, University of Western AustraliaDepartment of Genetics, University Medical Center UtrechtDepartment of Surgery, Perelman School of Medicine, University of PennsylvaniaAbstract 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.https://doi.org/10.1038/s41598-023-49105-1 |
| spellingShingle | Amein K. Al-Ali Abdullah M. Al-Rubaish Rudaynah A. Alali Mohammed S. Almansori Mohammed A. Al-Jumaan Abdullah M. Alshehri Mohammed S. Al-Madan ChittiBabu Vatte Tess Cherlin Sylvia Young Shefali S. Verma Grant Morahan Bobby P. C. Koeleman Brendan J. Keating Uncovering myocardial infarction genetic signatures using GWAS exploration in Saudi and European cohorts Scientific Reports |
| title | Uncovering myocardial infarction genetic signatures using GWAS exploration in Saudi and European cohorts |
| title_full | Uncovering myocardial infarction genetic signatures using GWAS exploration in Saudi and European cohorts |
| title_fullStr | Uncovering myocardial infarction genetic signatures using GWAS exploration in Saudi and European cohorts |
| title_full_unstemmed | Uncovering myocardial infarction genetic signatures using GWAS exploration in Saudi and European cohorts |
| title_short | Uncovering myocardial infarction genetic signatures using GWAS exploration in Saudi and European cohorts |
| title_sort | uncovering myocardial infarction genetic signatures using gwas exploration in saudi and european cohorts |
| url | https://doi.org/10.1038/s41598-023-49105-1 |
| work_keys_str_mv | AT ameinkalali uncoveringmyocardialinfarctiongeneticsignaturesusinggwasexplorationinsaudiandeuropeancohorts AT abdullahmalrubaish uncoveringmyocardialinfarctiongeneticsignaturesusinggwasexplorationinsaudiandeuropeancohorts AT rudaynahaalali uncoveringmyocardialinfarctiongeneticsignaturesusinggwasexplorationinsaudiandeuropeancohorts AT mohammedsalmansori uncoveringmyocardialinfarctiongeneticsignaturesusinggwasexplorationinsaudiandeuropeancohorts AT mohammedaaljumaan uncoveringmyocardialinfarctiongeneticsignaturesusinggwasexplorationinsaudiandeuropeancohorts AT abdullahmalshehri uncoveringmyocardialinfarctiongeneticsignaturesusinggwasexplorationinsaudiandeuropeancohorts AT mohammedsalmadan uncoveringmyocardialinfarctiongeneticsignaturesusinggwasexplorationinsaudiandeuropeancohorts AT chittibabuvatte uncoveringmyocardialinfarctiongeneticsignaturesusinggwasexplorationinsaudiandeuropeancohorts AT tesscherlin uncoveringmyocardialinfarctiongeneticsignaturesusinggwasexplorationinsaudiandeuropeancohorts AT sylviayoung uncoveringmyocardialinfarctiongeneticsignaturesusinggwasexplorationinsaudiandeuropeancohorts AT shefalisverma uncoveringmyocardialinfarctiongeneticsignaturesusinggwasexplorationinsaudiandeuropeancohorts AT grantmorahan uncoveringmyocardialinfarctiongeneticsignaturesusinggwasexplorationinsaudiandeuropeancohorts AT bobbypckoeleman uncoveringmyocardialinfarctiongeneticsignaturesusinggwasexplorationinsaudiandeuropeancohorts AT brendanjkeating uncoveringmyocardialinfarctiongeneticsignaturesusinggwasexplorationinsaudiandeuropeancohorts |