Polygenic risk of prediabetes, undiagnosed diabetes, and incident type 2 diabetes stratified by diabetes risk factors
<p><strong>Context:</strong> Early diagnosis of type 2 diabetes is crucial to reduce severe comorbidities and complications. Current screening recommendations for type 2 diabetes include traditional risk factors, primarily body mass index (BMI) and family history, however genetics...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Oxford University Press
2023
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| _version_ | 1797109605721964544 |
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| author | Liu, X Collister, JA Clifton, L Hunter, DJ Littlejohns, TJ |
| author_facet | Liu, X Collister, JA Clifton, L Hunter, DJ Littlejohns, TJ |
| author_sort | Liu, X |
| collection | OXFORD |
| description | <p><strong>Context:</strong> Early diagnosis of type 2 diabetes is crucial to reduce severe comorbidities and complications. Current screening recommendations for type 2 diabetes include traditional risk factors, primarily body mass index (BMI) and family history, however genetics also plays a key role in type 2 diabetes risk. It is important to understand whether genetic predisposition to type 2 diabetes modifies the effect of these traditional factors on type 2 diabetes risk.</p>
<p><strong>Objective:</strong> This work aimed to investigate whether genetic risk of type 2 diabetes modifies associations between BMI and first-degree family history of diabetes with 1) prevalent prediabetes or undiagnosed diabetes; and 2) incident confirmed type 2 diabetes.</p>
<p><strong>Methods:</strong> We included 431 658 individuals aged 40 to 69 years at baseline of multiethnic ancestry from the UK Biobank. We used a multiethnic polygenic risk score for type 2 diabetes (PRS<sub>T2D</sub>) developed by Genomics PLC. Prediabetes or undiagnosed diabetes was defined as baseline glycated hemoglobin greater than or equal to 42 mmol/mol (6.0%), and incident type 2 diabetes was derived from medical records.</p>
<p><strong>Results:</strong> At baseline, 43 472 participants had prediabetes or undiagnosed diabetes, and 17 259 developed type 2 diabetes over 15 years follow-up. Dose-response associations were observed for PRS<sub>T2D</sub> with each outcome in each category of BMI or first-degree family history of diabetes. Those in the highest quintile of PRS<sub>T2D</sub> with a normal BMI were at a similar risk as those in the middle quintile who were overweight. Participants who were in the highest quintile of PRS<sub>T2D</sub> and did not have a first-degree family history of diabetes were at a similar risk as those with a family history who were in the middle category of PRS<sub>T2D</sub>.</p>
<p><strong>Conclusion:</strong> Genetic risk of type 2 diabetes remains strongly associated with risk of prediabetes, undiagnosed diabetes, and future type 2 diabetes within categories of nongenetic risk factors. This could have important implications for identifying individuals at risk of type 2 diabetes for prevention and early diagnosis programs.</p> |
| first_indexed | 2024-03-07T07:43:58Z |
| format | Journal article |
| id | oxford-uuid:73f88b48-7f71-42f2-a82d-1d2f441c4d46 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:43:58Z |
| publishDate | 2023 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:73f88b48-7f71-42f2-a82d-1d2f441c4d462023-05-23T16:53:17ZPolygenic risk of prediabetes, undiagnosed diabetes, and incident type 2 diabetes stratified by diabetes risk factorsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:73f88b48-7f71-42f2-a82d-1d2f441c4d46EnglishSymplectic Elements Oxford University Press2023Liu, XCollister, JAClifton, LHunter, DJLittlejohns, TJ<p><strong>Context:</strong> Early diagnosis of type 2 diabetes is crucial to reduce severe comorbidities and complications. Current screening recommendations for type 2 diabetes include traditional risk factors, primarily body mass index (BMI) and family history, however genetics also plays a key role in type 2 diabetes risk. It is important to understand whether genetic predisposition to type 2 diabetes modifies the effect of these traditional factors on type 2 diabetes risk.</p> <p><strong>Objective:</strong> This work aimed to investigate whether genetic risk of type 2 diabetes modifies associations between BMI and first-degree family history of diabetes with 1) prevalent prediabetes or undiagnosed diabetes; and 2) incident confirmed type 2 diabetes.</p> <p><strong>Methods:</strong> We included 431 658 individuals aged 40 to 69 years at baseline of multiethnic ancestry from the UK Biobank. We used a multiethnic polygenic risk score for type 2 diabetes (PRS<sub>T2D</sub>) developed by Genomics PLC. Prediabetes or undiagnosed diabetes was defined as baseline glycated hemoglobin greater than or equal to 42 mmol/mol (6.0%), and incident type 2 diabetes was derived from medical records.</p> <p><strong>Results:</strong> At baseline, 43 472 participants had prediabetes or undiagnosed diabetes, and 17 259 developed type 2 diabetes over 15 years follow-up. Dose-response associations were observed for PRS<sub>T2D</sub> with each outcome in each category of BMI or first-degree family history of diabetes. Those in the highest quintile of PRS<sub>T2D</sub> with a normal BMI were at a similar risk as those in the middle quintile who were overweight. Participants who were in the highest quintile of PRS<sub>T2D</sub> and did not have a first-degree family history of diabetes were at a similar risk as those with a family history who were in the middle category of PRS<sub>T2D</sub>.</p> <p><strong>Conclusion:</strong> Genetic risk of type 2 diabetes remains strongly associated with risk of prediabetes, undiagnosed diabetes, and future type 2 diabetes within categories of nongenetic risk factors. This could have important implications for identifying individuals at risk of type 2 diabetes for prevention and early diagnosis programs.</p> |
| spellingShingle | Liu, X Collister, JA Clifton, L Hunter, DJ Littlejohns, TJ Polygenic risk of prediabetes, undiagnosed diabetes, and incident type 2 diabetes stratified by diabetes risk factors |
| title | Polygenic risk of prediabetes, undiagnosed diabetes, and incident type 2 diabetes stratified by diabetes risk factors |
| title_full | Polygenic risk of prediabetes, undiagnosed diabetes, and incident type 2 diabetes stratified by diabetes risk factors |
| title_fullStr | Polygenic risk of prediabetes, undiagnosed diabetes, and incident type 2 diabetes stratified by diabetes risk factors |
| title_full_unstemmed | Polygenic risk of prediabetes, undiagnosed diabetes, and incident type 2 diabetes stratified by diabetes risk factors |
| title_short | Polygenic risk of prediabetes, undiagnosed diabetes, and incident type 2 diabetes stratified by diabetes risk factors |
| title_sort | polygenic risk of prediabetes undiagnosed diabetes and incident type 2 diabetes stratified by diabetes risk factors |
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