Genome-wide association study and polygenic score assessment of insulin resistance
<p dir="ltr">Insulin resistance (IR) and beta cell dysfunction are the major drivers of type 2 diabetes (T2D). Genome-Wide Association Studies (GWAS) on IR have been predominantly conducted in European populations, while Middle Eastern populations remain largely underrepresented. We...
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| مؤلفون آخرون: | , , , , , , |
| منشور في: |
2024
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| _version_ | 1864513509745754112 |
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| author | Usama Aliyu (19325605) |
| author2 | Umm-Kulthum Ismail Umlai (12040352) Salman M. Toor (8854751) Asma A. Elashi (17821415) Yasser A. Al-Sarraj (9452585) Abdul Badi Abou−Samra (19325608) Karsten Suhre (67967) Omar M. E. Albagha (11704871) |
| author2_role | author author author author author author author |
| author_facet | Usama Aliyu (19325605) Umm-Kulthum Ismail Umlai (12040352) Salman M. Toor (8854751) Asma A. Elashi (17821415) Yasser A. Al-Sarraj (9452585) Abdul Badi Abou−Samra (19325608) Karsten Suhre (67967) Omar M. E. Albagha (11704871) |
| author_role | author |
| dc.creator.none.fl_str_mv | Usama Aliyu (19325605) Umm-Kulthum Ismail Umlai (12040352) Salman M. Toor (8854751) Asma A. Elashi (17821415) Yasser A. Al-Sarraj (9452585) Abdul Badi Abou−Samra (19325608) Karsten Suhre (67967) Omar M. E. Albagha (11704871) |
| dc.date.none.fl_str_mv | 2024-06-13T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3389/fendo.2024.1384103 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Genome-wide_association_study_and_polygenic_score_assessment_of_insulin_resistance/26490847 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Health sciences Epidemiology insulin resistance beta cell type 2 diabetes GWAS polygenic score |
| dc.title.none.fl_str_mv | Genome-wide association study and polygenic score assessment of insulin resistance |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Insulin resistance (IR) and beta cell dysfunction are the major drivers of type 2 diabetes (T2D). Genome-Wide Association Studies (GWAS) on IR have been predominantly conducted in European populations, while Middle Eastern populations remain largely underrepresented. We conducted a GWAS on the indices of IR (HOMA2-IR) and beta cell function (HOMA2-%B) in 6,217 non-diabetic individuals from the Qatar Biobank (QBB; Discovery cohort; n = 2170, Replication cohort; n = 4047) with and without body mass index (BMI) adjustment. We also developed polygenic scores (PGS) for HOMA2-IR and compared their performance with a previously derived PGS for HOMA-IR (PGS003470). We replicated 11 loci that have been previously associated with HOMA-IR and 24 loci that have been associated with HOMA-%B, at nominal statistical significance. We also identified a novel locus associated with beta cell function near VEGFC gene, tagged by rs61552983 (P = 4.38 × 10<sup>-8</sup>). Moreover, our best performing PGS (Q-PGS4; Adj R<sup>2</sup> = 0.233 ± 0.014; P = 1.55 x 10-3) performed better than PGS003470 (Adj R<sup>2</sup> = 0.194 ± 0.014; <i>P</i> = 5.45 x 10<sup>-2</sup>) in predicting HOMA2-IR in our dataset. This is the first GWAS on HOMA2 and the first GWAS conducted in the Middle East focusing on IR and beta cell function. Herein, we report a novel locus in VEGFC that is implicated in beta cell dysfunction. Inclusion of under-represented populations in GWAS has potentials to provide important insights into the genetic architecture of IR and beta cell function.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Endocrinology<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/10.3389/fendo.2024.1384103" target="_blank">https://dx.doi.org/10.3389/fendo.2024.1384103</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_db5af03a1b94b78ff2fc2311ba7069e9 |
| identifier_str_mv | 10.3389/fendo.2024.1384103 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26490847 |
| 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 polygenic score assessment of insulin resistanceUsama Aliyu (19325605)Umm-Kulthum Ismail Umlai (12040352)Salman M. Toor (8854751)Asma A. Elashi (17821415)Yasser A. Al-Sarraj (9452585)Abdul Badi Abou−Samra (19325608)Karsten Suhre (67967)Omar M. E. Albagha (11704871)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesMedical biochemistry and metabolomicsHealth sciencesEpidemiologyinsulin resistancebeta celltype 2 diabetesGWASpolygenic score<p dir="ltr">Insulin resistance (IR) and beta cell dysfunction are the major drivers of type 2 diabetes (T2D). Genome-Wide Association Studies (GWAS) on IR have been predominantly conducted in European populations, while Middle Eastern populations remain largely underrepresented. We conducted a GWAS on the indices of IR (HOMA2-IR) and beta cell function (HOMA2-%B) in 6,217 non-diabetic individuals from the Qatar Biobank (QBB; Discovery cohort; n = 2170, Replication cohort; n = 4047) with and without body mass index (BMI) adjustment. We also developed polygenic scores (PGS) for HOMA2-IR and compared their performance with a previously derived PGS for HOMA-IR (PGS003470). We replicated 11 loci that have been previously associated with HOMA-IR and 24 loci that have been associated with HOMA-%B, at nominal statistical significance. We also identified a novel locus associated with beta cell function near VEGFC gene, tagged by rs61552983 (P = 4.38 × 10<sup>-8</sup>). Moreover, our best performing PGS (Q-PGS4; Adj R<sup>2</sup> = 0.233 ± 0.014; P = 1.55 x 10-3) performed better than PGS003470 (Adj R<sup>2</sup> = 0.194 ± 0.014; <i>P</i> = 5.45 x 10<sup>-2</sup>) in predicting HOMA2-IR in our dataset. This is the first GWAS on HOMA2 and the first GWAS conducted in the Middle East focusing on IR and beta cell function. Herein, we report a novel locus in VEGFC that is implicated in beta cell dysfunction. Inclusion of under-represented populations in GWAS has potentials to provide important insights into the genetic architecture of IR and beta cell function.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Endocrinology<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/10.3389/fendo.2024.1384103" target="_blank">https://dx.doi.org/10.3389/fendo.2024.1384103</a></p>2024-06-13T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fendo.2024.1384103https://figshare.com/articles/journal_contribution/Genome-wide_association_study_and_polygenic_score_assessment_of_insulin_resistance/26490847CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/264908472024-06-13T09:00:00Z |
| spellingShingle | Genome-wide association study and polygenic score assessment of insulin resistance Usama Aliyu (19325605) Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Health sciences Epidemiology insulin resistance beta cell type 2 diabetes GWAS polygenic score |
| status_str | publishedVersion |
| title | Genome-wide association study and polygenic score assessment of insulin resistance |
| title_full | Genome-wide association study and polygenic score assessment of insulin resistance |
| title_fullStr | Genome-wide association study and polygenic score assessment of insulin resistance |
| title_full_unstemmed | Genome-wide association study and polygenic score assessment of insulin resistance |
| title_short | Genome-wide association study and polygenic score assessment of insulin resistance |
| title_sort | Genome-wide association study and polygenic score assessment of insulin resistance |
| topic | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Health sciences Epidemiology insulin resistance beta cell type 2 diabetes GWAS polygenic score |