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A Polygenic Score for Type 2 Diabetes Improves Risk Stratification Beyond Current Clinical Screening Factors in an Ancestrally Diverse Sample

A substantial proportion of the adult United States population with type 2 diabetes (T2D) are undiagnosed, calling into question the comprehensiveness of current screening practices, which primarily rely on age, family history, and body mass index (BMI). We hypothesized that a polygenic score (PGS)...

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Autores principales: Ashenhurst, James R., Sazonova, Olga V., Svrchek, Olivia, Detweiler, Stacey, Kita, Ryosuke, Babalola, Liz, McIntyre, Matthew, Aslibekyan, Stella, Fontanillas, Pierre, Shringarpure, Suyash, Pollard, Jeffrey D., Koelsch, Bertram L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086969/
https://www.ncbi.nlm.nih.gov/pubmed/35559025
http://dx.doi.org/10.3389/fgene.2022.871260
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author Ashenhurst, James R.
Sazonova, Olga V.
Svrchek, Olivia
Detweiler, Stacey
Kita, Ryosuke
Babalola, Liz
McIntyre, Matthew
Aslibekyan, Stella
Fontanillas, Pierre
Shringarpure, Suyash
Pollard, Jeffrey D.
Koelsch, Bertram L.
author_facet Ashenhurst, James R.
Sazonova, Olga V.
Svrchek, Olivia
Detweiler, Stacey
Kita, Ryosuke
Babalola, Liz
McIntyre, Matthew
Aslibekyan, Stella
Fontanillas, Pierre
Shringarpure, Suyash
Pollard, Jeffrey D.
Koelsch, Bertram L.
author_sort Ashenhurst, James R.
collection PubMed
description A substantial proportion of the adult United States population with type 2 diabetes (T2D) are undiagnosed, calling into question the comprehensiveness of current screening practices, which primarily rely on age, family history, and body mass index (BMI). We hypothesized that a polygenic score (PGS) may serve as a complementary tool to identify high-risk individuals. The T2D polygenic score maintained predictive utility after adjusting for family history and combining genetics with family history led to even more improved disease risk prediction. We observed that the PGS was meaningfully related to age of onset with implications for screening practices: there was a linear and statistically significant relationship between the PGS and T2D onset (−1.3 years per standard deviation of the PGS). Evaluation of U.S. Preventive Task Force and a simplified version of American Diabetes Association screening guidelines showed that addition of a screening criterion for those above the 90th percentile of the PGS provided a small increase the sensitivity of the screening algorithm. Among T2D-negative individuals, the T2D PGS was associated with prediabetes, where each standard deviation increase of the PGS was associated with a 23% increase in the odds of prediabetes diagnosis. Additionally, each standard deviation increase in the PGS corresponded to a 43% increase in the odds of incident T2D at one-year follow-up. Using complications and forms of clinical intervention (i.e., lifestyle modification, metformin treatment, or insulin treatment) as proxies for advanced illness we also found statistically significant associations between the T2D PGS and insulin treatment and diabetic neuropathy. Importantly, we were able to replicate many findings in a Hispanic/Latino cohort from our database, highlighting the value of the T2D PGS as a clinical tool for individuals with ancestry other than European. In this group, the T2D PGS provided additional disease risk information beyond that offered by traditional screening methodologies. The T2D PGS also had predictive value for the age of onset and for prediabetes among T2D-negative Hispanic/Latino participants. These findings strengthen the notion that a T2D PGS could play a role in the clinical setting across multiple ancestries, potentially improving T2D screening practices, risk stratification, and disease management.
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spelling pubmed-90869692022-05-11 A Polygenic Score for Type 2 Diabetes Improves Risk Stratification Beyond Current Clinical Screening Factors in an Ancestrally Diverse Sample Ashenhurst, James R. Sazonova, Olga V. Svrchek, Olivia Detweiler, Stacey Kita, Ryosuke Babalola, Liz McIntyre, Matthew Aslibekyan, Stella Fontanillas, Pierre Shringarpure, Suyash Pollard, Jeffrey D. Koelsch, Bertram L. Front Genet Genetics A substantial proportion of the adult United States population with type 2 diabetes (T2D) are undiagnosed, calling into question the comprehensiveness of current screening practices, which primarily rely on age, family history, and body mass index (BMI). We hypothesized that a polygenic score (PGS) may serve as a complementary tool to identify high-risk individuals. The T2D polygenic score maintained predictive utility after adjusting for family history and combining genetics with family history led to even more improved disease risk prediction. We observed that the PGS was meaningfully related to age of onset with implications for screening practices: there was a linear and statistically significant relationship between the PGS and T2D onset (−1.3 years per standard deviation of the PGS). Evaluation of U.S. Preventive Task Force and a simplified version of American Diabetes Association screening guidelines showed that addition of a screening criterion for those above the 90th percentile of the PGS provided a small increase the sensitivity of the screening algorithm. Among T2D-negative individuals, the T2D PGS was associated with prediabetes, where each standard deviation increase of the PGS was associated with a 23% increase in the odds of prediabetes diagnosis. Additionally, each standard deviation increase in the PGS corresponded to a 43% increase in the odds of incident T2D at one-year follow-up. Using complications and forms of clinical intervention (i.e., lifestyle modification, metformin treatment, or insulin treatment) as proxies for advanced illness we also found statistically significant associations between the T2D PGS and insulin treatment and diabetic neuropathy. Importantly, we were able to replicate many findings in a Hispanic/Latino cohort from our database, highlighting the value of the T2D PGS as a clinical tool for individuals with ancestry other than European. In this group, the T2D PGS provided additional disease risk information beyond that offered by traditional screening methodologies. The T2D PGS also had predictive value for the age of onset and for prediabetes among T2D-negative Hispanic/Latino participants. These findings strengthen the notion that a T2D PGS could play a role in the clinical setting across multiple ancestries, potentially improving T2D screening practices, risk stratification, and disease management. Frontiers Media S.A. 2022-04-26 /pmc/articles/PMC9086969/ /pubmed/35559025 http://dx.doi.org/10.3389/fgene.2022.871260 Text en Copyright © 2022 Ashenhurst, Sazonova, Svrchek, Detweiler, Kita, Babalola, McIntyre, Aslibekyan, Fontanillas, Shringarpure, Pollard and Koelsch. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Ashenhurst, James R.
Sazonova, Olga V.
Svrchek, Olivia
Detweiler, Stacey
Kita, Ryosuke
Babalola, Liz
McIntyre, Matthew
Aslibekyan, Stella
Fontanillas, Pierre
Shringarpure, Suyash
Pollard, Jeffrey D.
Koelsch, Bertram L.
A Polygenic Score for Type 2 Diabetes Improves Risk Stratification Beyond Current Clinical Screening Factors in an Ancestrally Diverse Sample
title A Polygenic Score for Type 2 Diabetes Improves Risk Stratification Beyond Current Clinical Screening Factors in an Ancestrally Diverse Sample
title_full A Polygenic Score for Type 2 Diabetes Improves Risk Stratification Beyond Current Clinical Screening Factors in an Ancestrally Diverse Sample
title_fullStr A Polygenic Score for Type 2 Diabetes Improves Risk Stratification Beyond Current Clinical Screening Factors in an Ancestrally Diverse Sample
title_full_unstemmed A Polygenic Score for Type 2 Diabetes Improves Risk Stratification Beyond Current Clinical Screening Factors in an Ancestrally Diverse Sample
title_short A Polygenic Score for Type 2 Diabetes Improves Risk Stratification Beyond Current Clinical Screening Factors in an Ancestrally Diverse Sample
title_sort polygenic score for type 2 diabetes improves risk stratification beyond current clinical screening factors in an ancestrally diverse sample
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086969/
https://www.ncbi.nlm.nih.gov/pubmed/35559025
http://dx.doi.org/10.3389/fgene.2022.871260
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