Evaluating the Efficacy of Type 2 Diabetes Polygenic Risk Scores in an Independent European Population
Numerous type 2 diabetes (T2D) polygenic risk scores (PGSs) have been developed to predict individuals’ predisposition to the disease. An independent assessment and verification of the best-performing PGS are warranted to allow for a rapid application of developed models. To date, only 3% of T2D PGS...
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| Format: | Article |
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/2/1151 |
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| author | Monta Brīvība Ivanna Atava Raitis Pečulis Ilze Elbere Laura Ansone Maija Rozenberga Ivars Silamiķelis Jānis Kloviņš |
| author_facet | Monta Brīvība Ivanna Atava Raitis Pečulis Ilze Elbere Laura Ansone Maija Rozenberga Ivars Silamiķelis Jānis Kloviņš |
| author_sort | Monta Brīvība |
| collection | DOAJ |
| description | Numerous type 2 diabetes (T2D) polygenic risk scores (PGSs) have been developed to predict individuals’ predisposition to the disease. An independent assessment and verification of the best-performing PGS are warranted to allow for a rapid application of developed models. To date, only 3% of T2D PGSs have been evaluated. In this study, we assessed all (n = 102) presently published T2D PGSs in an independent cohort of 3718 individuals, which has not been included in the construction or fine-tuning of any T2D PGS so far. We further chose the best-performing PGS, assessed its performance across major population principal component analysis (PCA) clusters, and compared it with newly developed population-specific T2D PGS. Our findings revealed that 88% of the published PGSs were significantly associated with T2D; however, their performance was lower than what had been previously reported. We found a positive association of PGS improvement over the years (<i>p</i>-value = 8.01 × 10<sup>−4</sup> with PGS002771 currently showing the best discriminatory power (area under the receiver operating characteristic (AUROC) = 0.669) and PGS003443 exhibiting the strongest association PGS003443 (odds ratio (OR) = 1.899). Further investigation revealed no difference in PGS performance across major population PCA clusters and when compared with newly developed population-specific PGS. Our findings revealed a positive trend in T2D PGS performance, consistently identifying high-T2D-risk individuals in an independent European population. |
| first_indexed | 2024-03-08T09:53:12Z |
| format | Article |
| id | doaj.art-be1bf08149234e0bb2b6a51c4331d1fb |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T09:53:12Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-be1bf08149234e0bb2b6a51c4331d1fb2024-01-29T13:57:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-01252115110.3390/ijms25021151Evaluating the Efficacy of Type 2 Diabetes Polygenic Risk Scores in an Independent European PopulationMonta Brīvība0Ivanna Atava1Raitis Pečulis2Ilze Elbere3Laura Ansone4Maija Rozenberga5Ivars Silamiķelis6Jānis Kloviņš7Latvian Biomedical Research and Study Centre, LV-1067 Riga, LatviaLatvian Biomedical Research and Study Centre, LV-1067 Riga, LatviaLatvian Biomedical Research and Study Centre, LV-1067 Riga, LatviaLatvian Biomedical Research and Study Centre, LV-1067 Riga, LatviaLatvian Biomedical Research and Study Centre, LV-1067 Riga, LatviaLatvian Biomedical Research and Study Centre, LV-1067 Riga, LatviaLatvian Biomedical Research and Study Centre, LV-1067 Riga, LatviaLatvian Biomedical Research and Study Centre, LV-1067 Riga, LatviaNumerous type 2 diabetes (T2D) polygenic risk scores (PGSs) have been developed to predict individuals’ predisposition to the disease. An independent assessment and verification of the best-performing PGS are warranted to allow for a rapid application of developed models. To date, only 3% of T2D PGSs have been evaluated. In this study, we assessed all (n = 102) presently published T2D PGSs in an independent cohort of 3718 individuals, which has not been included in the construction or fine-tuning of any T2D PGS so far. We further chose the best-performing PGS, assessed its performance across major population principal component analysis (PCA) clusters, and compared it with newly developed population-specific T2D PGS. Our findings revealed that 88% of the published PGSs were significantly associated with T2D; however, their performance was lower than what had been previously reported. We found a positive association of PGS improvement over the years (<i>p</i>-value = 8.01 × 10<sup>−4</sup> with PGS002771 currently showing the best discriminatory power (area under the receiver operating characteristic (AUROC) = 0.669) and PGS003443 exhibiting the strongest association PGS003443 (odds ratio (OR) = 1.899). Further investigation revealed no difference in PGS performance across major population PCA clusters and when compared with newly developed population-specific PGS. Our findings revealed a positive trend in T2D PGS performance, consistently identifying high-T2D-risk individuals in an independent European population.https://www.mdpi.com/1422-0067/25/2/1151type 2 diabetespolygenic risk scorepopulation stratification |
| spellingShingle | Monta Brīvība Ivanna Atava Raitis Pečulis Ilze Elbere Laura Ansone Maija Rozenberga Ivars Silamiķelis Jānis Kloviņš Evaluating the Efficacy of Type 2 Diabetes Polygenic Risk Scores in an Independent European Population International Journal of Molecular Sciences type 2 diabetes polygenic risk score population stratification |
| title | Evaluating the Efficacy of Type 2 Diabetes Polygenic Risk Scores in an Independent European Population |
| title_full | Evaluating the Efficacy of Type 2 Diabetes Polygenic Risk Scores in an Independent European Population |
| title_fullStr | Evaluating the Efficacy of Type 2 Diabetes Polygenic Risk Scores in an Independent European Population |
| title_full_unstemmed | Evaluating the Efficacy of Type 2 Diabetes Polygenic Risk Scores in an Independent European Population |
| title_short | Evaluating the Efficacy of Type 2 Diabetes Polygenic Risk Scores in an Independent European Population |
| title_sort | evaluating the efficacy of type 2 diabetes polygenic risk scores in an independent european population |
| topic | type 2 diabetes polygenic risk score population stratification |
| url | https://www.mdpi.com/1422-0067/25/2/1151 |
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