Polygenic risk for type 2 diabetes, lifestyle, metabolic health, and cardiovascular disease: a prospective UK Biobank study
Abstract Background Few studies have examined associations between genetic risk for type 2 diabetes (T2D), lifestyle, clinical risk factors, and cardiovascular disease (CVD). We aimed to investigate the association of and potential interactions among genetic risk for T2D, lifestyle behavior, and met...
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12933-022-01560-2 |
| _version_ | 1828747133053829120 |
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| author | Jae-Seung Yun Sang-Hyuk Jung Manu Shivakumar Brenda Xiao Amit V. Khera Hong-Hee Won Dokyoon Kim |
| author_facet | Jae-Seung Yun Sang-Hyuk Jung Manu Shivakumar Brenda Xiao Amit V. Khera Hong-Hee Won Dokyoon Kim |
| author_sort | Jae-Seung Yun |
| collection | DOAJ |
| description | Abstract Background Few studies have examined associations between genetic risk for type 2 diabetes (T2D), lifestyle, clinical risk factors, and cardiovascular disease (CVD). We aimed to investigate the association of and potential interactions among genetic risk for T2D, lifestyle behavior, and metabolic risk factors with CVD. Methods A total of 345,217 unrelated participants of white British descent were included in analyses. Genetic risk for T2D was estimated as a genome-wide polygenic risk score constructed from > 6 million genetic variants. A favorable lifestyle was defined in terms of four modifiable lifestyle components, and metabolic health status was determined according to the presence of metabolic syndrome components. Results During a median follow-up of 8.9 years, 21,865 CVD cases (6.3%) were identified. Compared with the low genetic risk group, participants at high genetic risk for T2D had higher rates of overall CVD events, CVD subtypes (coronary artery disease, peripheral artery disease, heart failure, and atrial fibrillation/flutter), and CVD mortality. Individuals at very high genetic risk for T2D had a 35% higher risk of CVD than those with low genetic risk (HR 1.35 [95% CI 1.19 to 1.53]). A significant gradient of increased CVD risk was observed across genetic risk, lifestyle, and metabolic health status (P for trend > 0.001). Those with favorable lifestyle and metabolically healthy status had significantly reduced risk of CVD events regardless of T2D genetic risk. This risk reduction was more apparent in young participants (≤ 50 years). Conclusions Genetic risk for T2D was associated with increased risks of overall CVD, various CVD subtypes, and fatal CVD. Engaging in a healthy lifestyle and maintaining metabolic health may reduce subsequent risk of CVD regardless of genetic risk for T2D. |
| first_indexed | 2024-04-14T04:37:06Z |
| format | Article |
| id | doaj.art-73e788d15b10429dbda623e219670bd5 |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-04-14T04:37:06Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-73e788d15b10429dbda623e219670bd52022-12-22T02:11:49ZengBMCCardiovascular Diabetology1475-28402022-07-0121111110.1186/s12933-022-01560-2Polygenic risk for type 2 diabetes, lifestyle, metabolic health, and cardiovascular disease: a prospective UK Biobank studyJae-Seung Yun0Sang-Hyuk Jung1Manu Shivakumar2Brenda Xiao3Amit V. Khera4Hong-Hee Won5Dokyoon Kim6Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of PennsylvaniaDepartment of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of PennsylvaniaDepartment of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of PennsylvaniaDepartment of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of PennsylvaniaCenter for Genomic Medicine, Massachusetts General HospitalSamsung Advanced Institute for Health Sciences and Technology (SAIHST), Samsung Medical Center, Sungkyunkwan UniversityDepartment of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of PennsylvaniaAbstract Background Few studies have examined associations between genetic risk for type 2 diabetes (T2D), lifestyle, clinical risk factors, and cardiovascular disease (CVD). We aimed to investigate the association of and potential interactions among genetic risk for T2D, lifestyle behavior, and metabolic risk factors with CVD. Methods A total of 345,217 unrelated participants of white British descent were included in analyses. Genetic risk for T2D was estimated as a genome-wide polygenic risk score constructed from > 6 million genetic variants. A favorable lifestyle was defined in terms of four modifiable lifestyle components, and metabolic health status was determined according to the presence of metabolic syndrome components. Results During a median follow-up of 8.9 years, 21,865 CVD cases (6.3%) were identified. Compared with the low genetic risk group, participants at high genetic risk for T2D had higher rates of overall CVD events, CVD subtypes (coronary artery disease, peripheral artery disease, heart failure, and atrial fibrillation/flutter), and CVD mortality. Individuals at very high genetic risk for T2D had a 35% higher risk of CVD than those with low genetic risk (HR 1.35 [95% CI 1.19 to 1.53]). A significant gradient of increased CVD risk was observed across genetic risk, lifestyle, and metabolic health status (P for trend > 0.001). Those with favorable lifestyle and metabolically healthy status had significantly reduced risk of CVD events regardless of T2D genetic risk. This risk reduction was more apparent in young participants (≤ 50 years). Conclusions Genetic risk for T2D was associated with increased risks of overall CVD, various CVD subtypes, and fatal CVD. Engaging in a healthy lifestyle and maintaining metabolic health may reduce subsequent risk of CVD regardless of genetic risk for T2D.https://doi.org/10.1186/s12933-022-01560-2Polygenic risk scoreLifestyleMetabolic healthCardiovascular diseaseType 2 diabetes |
| spellingShingle | Jae-Seung Yun Sang-Hyuk Jung Manu Shivakumar Brenda Xiao Amit V. Khera Hong-Hee Won Dokyoon Kim Polygenic risk for type 2 diabetes, lifestyle, metabolic health, and cardiovascular disease: a prospective UK Biobank study Cardiovascular Diabetology Polygenic risk score Lifestyle Metabolic health Cardiovascular disease Type 2 diabetes |
| title | Polygenic risk for type 2 diabetes, lifestyle, metabolic health, and cardiovascular disease: a prospective UK Biobank study |
| title_full | Polygenic risk for type 2 diabetes, lifestyle, metabolic health, and cardiovascular disease: a prospective UK Biobank study |
| title_fullStr | Polygenic risk for type 2 diabetes, lifestyle, metabolic health, and cardiovascular disease: a prospective UK Biobank study |
| title_full_unstemmed | Polygenic risk for type 2 diabetes, lifestyle, metabolic health, and cardiovascular disease: a prospective UK Biobank study |
| title_short | Polygenic risk for type 2 diabetes, lifestyle, metabolic health, and cardiovascular disease: a prospective UK Biobank study |
| title_sort | polygenic risk for type 2 diabetes lifestyle metabolic health and cardiovascular disease a prospective uk biobank study |
| topic | Polygenic risk score Lifestyle Metabolic health Cardiovascular disease Type 2 diabetes |
| url | https://doi.org/10.1186/s12933-022-01560-2 |
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