<b>Development and Validation of a Type 1 Diabetes Multi-Ancestry Polygenic Score</b>
<p dir="ltr">Polygenic scores strongly predict type 1 diabetes risk, but most scores were developed in European-ancestry populations. In this study, we leveraged recent multi-ancestry genome-wide association studies to create a type 1 diabetes multi-ancestry polygenic score (T1D MAPS...
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2025
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| _version_ | 1849927630147551232 |
|---|---|
| author | Aaron J. Deutsch (15992555) |
| author2 | Andrew S. Bell (22377322) Dominika A. Michalek (22377324) Adam B. Burkholder (22377327) Stella Nam (22377328) Raymond J. Kreienkamp (22377330) Seth A. Sharp (22377331) Alicia Huerta-Chagoya (739312) Ravi Mandla (15992561) Ruth Nanjala (14709606) Yang Luo (350920) Richard A. Oram (21614925) Jose C. Florez (114792) Suna Onengut-Gumuscu (282049) Stephen S. Rich (110262) Maggie C. Y. Ng (190281) Alison A. Motsinger-Reif (22377334) Alisa K. Manning (110227) Josep M. Mercader (114767) Miriam S. Udler (15992566) |
| author2_role | author author author author author author author author author author author author author author author author author author author |
| author_facet | Aaron J. Deutsch (15992555) Andrew S. Bell (22377322) Dominika A. Michalek (22377324) Adam B. Burkholder (22377327) Stella Nam (22377328) Raymond J. Kreienkamp (22377330) Seth A. Sharp (22377331) Alicia Huerta-Chagoya (739312) Ravi Mandla (15992561) Ruth Nanjala (14709606) Yang Luo (350920) Richard A. Oram (21614925) Jose C. Florez (114792) Suna Onengut-Gumuscu (282049) Stephen S. Rich (110262) Maggie C. Y. Ng (190281) Alison A. Motsinger-Reif (22377334) Alisa K. Manning (110227) Josep M. Mercader (114767) Miriam S. Udler (15992566) |
| author_role | author |
| dc.creator.none.fl_str_mv | Aaron J. Deutsch (15992555) Andrew S. Bell (22377322) Dominika A. Michalek (22377324) Adam B. Burkholder (22377327) Stella Nam (22377328) Raymond J. Kreienkamp (22377330) Seth A. Sharp (22377331) Alicia Huerta-Chagoya (739312) Ravi Mandla (15992561) Ruth Nanjala (14709606) Yang Luo (350920) Richard A. Oram (21614925) Jose C. Florez (114792) Suna Onengut-Gumuscu (282049) Stephen S. Rich (110262) Maggie C. Y. Ng (190281) Alison A. Motsinger-Reif (22377334) Alisa K. Manning (110227) Josep M. Mercader (114767) Miriam S. Udler (15992566) |
| dc.date.none.fl_str_mv | 2025-11-25T16:11:35Z |
| dc.identifier.none.fl_str_mv | 10.2337/figshare.30286648.v2 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/figure/_b_Development_and_Validation_of_a_Type_1_Diabetes_Multi-Ancestry_Polygenic_Score_b_/30286648 |
| dc.rights.none.fl_str_mv | CC BY-NC-SA 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Other biological sciences not elsewhere classified Type 1 Diabetes Genetics Statistical Genetics Human Leukocyte Antigen (HLA) |
| dc.title.none.fl_str_mv | <b>Development and Validation of a Type 1 Diabetes Multi-Ancestry Polygenic Score</b> |
| dc.type.none.fl_str_mv | Image Figure info:eu-repo/semantics/publishedVersion image |
| description | <p dir="ltr">Polygenic scores strongly predict type 1 diabetes risk, but most scores were developed in European-ancestry populations. In this study, we leveraged recent multi-ancestry genome-wide association studies to create a type 1 diabetes multi-ancestry polygenic score (T1D MAPS). We trained the score in the Mass General Brigham (MGB) Biobank (372 individuals with type 1 diabetes) and tested the score in the All of Us program (86 individuals with type 1 diabetes). We evaluated the area under the receiver operating characteristic curve (AUC), and we compared the AUC to two published single-ancestry scores: T1D GRS2<sub>EUR</sub> and T1D GRS<sub>AFR</sub>. We also developed an updated score (T1D MAPS2) that combines T1D GRS2<sub>EUR</sub> and T1D MAPS. Among individuals with non-European ancestry, the AUC of T1D MAPS was 0.90, significantly higher than T1D GRS2<sub>EUR</sub> (0.82) and T1D GRS<sub>AFR</sub> (0.82). Among individuals with European ancestry, the AUC of T1D MAPS was slightly lower than T1D GRS2<sub>EUR</sub> (0.89 vs. 0.91). However, T1D MAPS2 performed equivalently to T1D GRS2<sub>EUR</sub> in European ancestry (0.91 vs. 0.91) and performed better in non-European ancestry (0.90 vs. 0.82). Overall, these findings advance the accuracy of type 1 diabetes genetic risk prediction across diverse populations.</p> |
| eu_rights_str_mv | openAccess |
| id | Manara_6ba25eccd5d0abee876b8bf7dccb0697 |
| identifier_str_mv | 10.2337/figshare.30286648.v2 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/30286648 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY-NC-SA 4.0 |
| spelling | <b>Development and Validation of a Type 1 Diabetes Multi-Ancestry Polygenic Score</b>Aaron J. Deutsch (15992555)Andrew S. Bell (22377322)Dominika A. Michalek (22377324)Adam B. Burkholder (22377327)Stella Nam (22377328)Raymond J. Kreienkamp (22377330)Seth A. Sharp (22377331)Alicia Huerta-Chagoya (739312)Ravi Mandla (15992561)Ruth Nanjala (14709606)Yang Luo (350920)Richard A. Oram (21614925)Jose C. Florez (114792)Suna Onengut-Gumuscu (282049)Stephen S. Rich (110262)Maggie C. Y. Ng (190281)Alison A. Motsinger-Reif (22377334)Alisa K. Manning (110227)Josep M. Mercader (114767)Miriam S. Udler (15992566)Other biological sciences not elsewhere classifiedType 1 DiabetesGeneticsStatistical GeneticsHuman Leukocyte Antigen (HLA)<p dir="ltr">Polygenic scores strongly predict type 1 diabetes risk, but most scores were developed in European-ancestry populations. In this study, we leveraged recent multi-ancestry genome-wide association studies to create a type 1 diabetes multi-ancestry polygenic score (T1D MAPS). We trained the score in the Mass General Brigham (MGB) Biobank (372 individuals with type 1 diabetes) and tested the score in the All of Us program (86 individuals with type 1 diabetes). We evaluated the area under the receiver operating characteristic curve (AUC), and we compared the AUC to two published single-ancestry scores: T1D GRS2<sub>EUR</sub> and T1D GRS<sub>AFR</sub>. We also developed an updated score (T1D MAPS2) that combines T1D GRS2<sub>EUR</sub> and T1D MAPS. Among individuals with non-European ancestry, the AUC of T1D MAPS was 0.90, significantly higher than T1D GRS2<sub>EUR</sub> (0.82) and T1D GRS<sub>AFR</sub> (0.82). Among individuals with European ancestry, the AUC of T1D MAPS was slightly lower than T1D GRS2<sub>EUR</sub> (0.89 vs. 0.91). However, T1D MAPS2 performed equivalently to T1D GRS2<sub>EUR</sub> in European ancestry (0.91 vs. 0.91) and performed better in non-European ancestry (0.90 vs. 0.82). Overall, these findings advance the accuracy of type 1 diabetes genetic risk prediction across diverse populations.</p>2025-11-25T16:11:35ZImageFigureinfo:eu-repo/semantics/publishedVersionimage10.2337/figshare.30286648.v2https://figshare.com/articles/figure/_b_Development_and_Validation_of_a_Type_1_Diabetes_Multi-Ancestry_Polygenic_Score_b_/30286648CC BY-NC-SA 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/302866482025-11-25T16:11:35Z |
| spellingShingle | <b>Development and Validation of a Type 1 Diabetes Multi-Ancestry Polygenic Score</b> Aaron J. Deutsch (15992555) Other biological sciences not elsewhere classified Type 1 Diabetes Genetics Statistical Genetics Human Leukocyte Antigen (HLA) |
| status_str | publishedVersion |
| title | <b>Development and Validation of a Type 1 Diabetes Multi-Ancestry Polygenic Score</b> |
| title_full | <b>Development and Validation of a Type 1 Diabetes Multi-Ancestry Polygenic Score</b> |
| title_fullStr | <b>Development and Validation of a Type 1 Diabetes Multi-Ancestry Polygenic Score</b> |
| title_full_unstemmed | <b>Development and Validation of a Type 1 Diabetes Multi-Ancestry Polygenic Score</b> |
| title_short | <b>Development and Validation of a Type 1 Diabetes Multi-Ancestry Polygenic Score</b> |
| title_sort | <b>Development and Validation of a Type 1 Diabetes Multi-Ancestry Polygenic Score</b> |
| topic | Other biological sciences not elsewhere classified Type 1 Diabetes Genetics Statistical Genetics Human Leukocyte Antigen (HLA) |