Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus
<h3>Background</h3><p dir="ltr">The genetic basis of type 2 diabetes (T2D) is under-investigated in the Middle East, despite the rapidly growing disease prevalence. We aimed to define the genetic determinants of T2D in Qatar.</p><h3>Methods</h3><p dir...
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| مؤلفون آخرون: | , , , , , , |
| منشور في: |
2024
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| الموضوعات: | |
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| _version_ | 1864513557150826496 |
|---|---|
| author | Asma A Elashi (18464133) |
| author2 | Salman M Toor (9279953) Umm-Kulthum Ismail Umlai (12040352) Yasser A Al-Sarraj (18464136) Shahrad Taheri (57360) Karsten Suhre (67967) Abdul Badi Abou-Samra (9417977) Omar M E Albagha (18295414) |
| author2_role | author author author author author author author |
| author_facet | Asma A Elashi (18464133) Salman M Toor (9279953) Umm-Kulthum Ismail Umlai (12040352) Yasser A Al-Sarraj (18464136) Shahrad Taheri (57360) Karsten Suhre (67967) Abdul Badi Abou-Samra (9417977) Omar M E Albagha (18295414) |
| author_role | author |
| dc.creator.none.fl_str_mv | Asma A Elashi (18464133) Salman M Toor (9279953) Umm-Kulthum Ismail Umlai (12040352) Yasser A Al-Sarraj (18464136) Shahrad Taheri (57360) Karsten Suhre (67967) Abdul Badi Abou-Samra (9417977) Omar M E Albagha (18295414) |
| dc.date.none.fl_str_mv | 2024-04-29T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1186/s12920-024-01855-1 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Genome-wide_association_study_and_trans-ethnic_meta-analysis_identify_novel_susceptibility_loci_for_type_2_diabetes_mellitus/27080779 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Bioinformatics and computational biology Genetics Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics GWAS Type 2 diabetes Mellitus T2D SNP TCF7L2 DYNC2H1 Polygenic risk score |
| dc.title.none.fl_str_mv | Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <h3>Background</h3><p dir="ltr">The genetic basis of type 2 diabetes (T2D) is under-investigated in the Middle East, despite the rapidly growing disease prevalence. We aimed to define the genetic determinants of T2D in Qatar.</p><h3>Methods</h3><p dir="ltr">Using whole genome sequencing of 11,436 participants (2765 T2D cases and 8671 controls) from the population-based Qatar Biobank (QBB), we conducted a genome-wide association study (GWAS) of T2D with and without body mass index (BMI) adjustment.</p><h3>Results</h3><p dir="ltr">We replicated 93 known T2D-associated loci in a BMI-unadjusted model, while 96 known loci were replicated in a BMI-adjusted model. The effect sizes and allele frequencies of replicated SNPs in the Qatari population generally concurred with those from European populations. We identified a locus specific to our cohort located between the APOBEC3H and CBX7 genes in the BMI-unadjusted model. Also, we performed a transethnic meta-analysis of our cohort with a previous GWAS on T2D in multi-ancestry individuals (180,834 T2D cases and 1,159,055 controls). One locus in DYNC2H1 gene reached genome-wide significance in the meta-analysis. Assessing polygenic risk scores derived from European- and multi-ancestries in the Qatari population showed higher predictive performance of the multi-ancestry panel compared to the European panel.</p><h3>Conclusion</h3><p dir="ltr">Our study provides new insights into the genetic architecture of T2D in a Middle Eastern population and identifies genes that may be explored further for their involvement in T2D pathogenesis.</p><p dir="ltr"><br></p><p dir="ltr">Correction: Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus: <a href="https://dx.doi.org/10.1186/s12920-024-01903-w" target="_blank">https://dx.doi.org/10.1186/s12920-024-01903-w</a>, published online 16 May 2024.</p><h2>Other Information</h2><p dir="ltr">Published in: BMC Medical Genomics<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12920-024-01855-1" target="_blank">https://dx.doi.org/10.1186/s12920-024-01855-1</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_191de02e6383a58eb5b99757c125fd1c |
| identifier_str_mv | 10.1186/s12920-024-01855-1 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/27080779 |
| publishDate | 2024 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitusAsma A Elashi (18464133)Salman M Toor (9279953)Umm-Kulthum Ismail Umlai (12040352)Yasser A Al-Sarraj (18464136)Shahrad Taheri (57360)Karsten Suhre (67967)Abdul Badi Abou-Samra (9417977)Omar M E Albagha (18295414)Biological sciencesBioinformatics and computational biologyGeneticsBiomedical and clinical sciencesClinical sciencesMedical biochemistry and metabolomicsGWASType 2 diabetes MellitusT2DSNPTCF7L2DYNC2H1Polygenic risk score<h3>Background</h3><p dir="ltr">The genetic basis of type 2 diabetes (T2D) is under-investigated in the Middle East, despite the rapidly growing disease prevalence. We aimed to define the genetic determinants of T2D in Qatar.</p><h3>Methods</h3><p dir="ltr">Using whole genome sequencing of 11,436 participants (2765 T2D cases and 8671 controls) from the population-based Qatar Biobank (QBB), we conducted a genome-wide association study (GWAS) of T2D with and without body mass index (BMI) adjustment.</p><h3>Results</h3><p dir="ltr">We replicated 93 known T2D-associated loci in a BMI-unadjusted model, while 96 known loci were replicated in a BMI-adjusted model. The effect sizes and allele frequencies of replicated SNPs in the Qatari population generally concurred with those from European populations. We identified a locus specific to our cohort located between the APOBEC3H and CBX7 genes in the BMI-unadjusted model. Also, we performed a transethnic meta-analysis of our cohort with a previous GWAS on T2D in multi-ancestry individuals (180,834 T2D cases and 1,159,055 controls). One locus in DYNC2H1 gene reached genome-wide significance in the meta-analysis. Assessing polygenic risk scores derived from European- and multi-ancestries in the Qatari population showed higher predictive performance of the multi-ancestry panel compared to the European panel.</p><h3>Conclusion</h3><p dir="ltr">Our study provides new insights into the genetic architecture of T2D in a Middle Eastern population and identifies genes that may be explored further for their involvement in T2D pathogenesis.</p><p dir="ltr"><br></p><p dir="ltr">Correction: Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus: <a href="https://dx.doi.org/10.1186/s12920-024-01903-w" target="_blank">https://dx.doi.org/10.1186/s12920-024-01903-w</a>, published online 16 May 2024.</p><h2>Other Information</h2><p dir="ltr">Published in: BMC Medical Genomics<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12920-024-01855-1" target="_blank">https://dx.doi.org/10.1186/s12920-024-01855-1</a></p>2024-04-29T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1186/s12920-024-01855-1https://figshare.com/articles/journal_contribution/Genome-wide_association_study_and_trans-ethnic_meta-analysis_identify_novel_susceptibility_loci_for_type_2_diabetes_mellitus/27080779CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/270807792024-04-29T09:00:00Z |
| spellingShingle | Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus Asma A Elashi (18464133) Biological sciences Bioinformatics and computational biology Genetics Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics GWAS Type 2 diabetes Mellitus T2D SNP TCF7L2 DYNC2H1 Polygenic risk score |
| status_str | publishedVersion |
| title | Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus |
| title_full | Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus |
| title_fullStr | Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus |
| title_full_unstemmed | Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus |
| title_short | Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus |
| title_sort | Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus |
| topic | Biological sciences Bioinformatics and computational biology Genetics Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics GWAS Type 2 diabetes Mellitus T2D SNP TCF7L2 DYNC2H1 Polygenic risk score |