Longitudinal Genome-Wide Association of Cardiovascular Disease Risk Factors in the Bogalusa Heart Study
Cardiovascular disease (CVD) is the leading cause of death worldwide. Recent genome-wide association (GWA) studies have pinpointed many loci associated with CVD risk factors in adults. It is unclear, however, if these loci predict trait levels at all ages, if they are associated with how a trait dev...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
| Published: |
2010
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| Online Access: | http://hdl.handle.net/1721.1/60304 |
| _version_ | 1811080054015262720 |
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| author | Peltonen, Leena Smith, Erin N. Chen, Wei Kahonen, Mika Kettunen, Johannes Lehtimaki, Terho Raitakari, Olli T. Salem, Rany M. Schork, Nicholas J. Shaw, Marian Srinivasan, Sathanur R. Topol, Eric J. Viikari, Jorma S. Berenson, Gerald S. Murray, Sarah S. |
| author2 | Peltonen, Leena |
| author_facet | Peltonen, Leena Peltonen, Leena Smith, Erin N. Chen, Wei Kahonen, Mika Kettunen, Johannes Lehtimaki, Terho Raitakari, Olli T. Salem, Rany M. Schork, Nicholas J. Shaw, Marian Srinivasan, Sathanur R. Topol, Eric J. Viikari, Jorma S. Berenson, Gerald S. Murray, Sarah S. |
| author_sort | Peltonen, Leena |
| collection | MIT |
| description | Cardiovascular disease (CVD) is the leading cause of death worldwide. Recent genome-wide association (GWA) studies have pinpointed many loci associated with CVD risk factors in adults. It is unclear, however, if these loci predict trait levels at all ages, if they are associated with how a trait develops over time, or if they could be used to screen individuals who are pre-symptomatic to provide the opportunity for preventive measures before disease onset. We completed a genome-wide association study on participants in the longitudinal Bogalusa Heart Study (BHS) and have characterized the association between genetic factors and the development of CVD risk factors from childhood to adulthood. We report 7 genome-wide significant associations involving CVD risk factors, two of which have been previously reported. Top regions were tested for replication in the Young Finns Study (YF) and two associations strongly replicated: rs247616 in CETP with HDL levels (combined P = 9.7×10[superscript −24]), and rs445925 at APOE with LDL levels (combined P = 8.7×10[superscript −19]). We show that SNPs previously identified in adult cross-sectional studies tend to show age-independent effects in the BHS with effect sizes consistent with previous reports. Previously identified variants were associated with adult trait levels above and beyond those seen in childhood; however, variants with time-dependent effects were also promising predictors. This is the first GWA study to evaluate the role of common genetic variants in the development of CVD risk factors in children as they advance through adulthood and highlights the utility of using longitudinal studies to identify genetic predictors of adult traits in children. |
| first_indexed | 2024-09-23T11:25:01Z |
| format | Article |
| id | mit-1721.1/60304 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:25:01Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | mit-1721.1/603042022-09-27T19:23:40Z Longitudinal Genome-Wide Association of Cardiovascular Disease Risk Factors in the Bogalusa Heart Study Peltonen, Leena Smith, Erin N. Chen, Wei Kahonen, Mika Kettunen, Johannes Lehtimaki, Terho Raitakari, Olli T. Salem, Rany M. Schork, Nicholas J. Shaw, Marian Srinivasan, Sathanur R. Topol, Eric J. Viikari, Jorma S. Berenson, Gerald S. Murray, Sarah S. Peltonen, Leena Peltonen, Leena Cardiovascular disease (CVD) is the leading cause of death worldwide. Recent genome-wide association (GWA) studies have pinpointed many loci associated with CVD risk factors in adults. It is unclear, however, if these loci predict trait levels at all ages, if they are associated with how a trait develops over time, or if they could be used to screen individuals who are pre-symptomatic to provide the opportunity for preventive measures before disease onset. We completed a genome-wide association study on participants in the longitudinal Bogalusa Heart Study (BHS) and have characterized the association between genetic factors and the development of CVD risk factors from childhood to adulthood. We report 7 genome-wide significant associations involving CVD risk factors, two of which have been previously reported. Top regions were tested for replication in the Young Finns Study (YF) and two associations strongly replicated: rs247616 in CETP with HDL levels (combined P = 9.7×10[superscript −24]), and rs445925 at APOE with LDL levels (combined P = 8.7×10[superscript −19]). We show that SNPs previously identified in adult cross-sectional studies tend to show age-independent effects in the BHS with effect sizes consistent with previous reports. Previously identified variants were associated with adult trait levels above and beyond those seen in childhood; however, variants with time-dependent effects were also promising predictors. This is the first GWA study to evaluate the role of common genetic variants in the development of CVD risk factors in children as they advance through adulthood and highlights the utility of using longitudinal studies to identify genetic predictors of adult traits in children. National Institutes of Health (U.S) (NIH 1U54RR025204-01) Academy of Finland (77841) Academy of Finland (210283) Academy of Finland (117832) Academy of Finland (121584) Social Insurance Institution of Finland Turku University Foundation Emil Aaltonen Foundation American Heart Association (0855082E) Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (HD-061437) National Institute of Aging (AG-16592) 2010-12-17T16:35:52Z 2010-12-17T16:35:52Z 2010-09 2010-03 Article http://purl.org/eprint/type/JournalArticle 1553-7404 1553-7390 http://hdl.handle.net/1721.1/60304 Smith EN, Chen W, Kähönen M, Kettunen J, Lehtimäki T, et al. 2010 Longitudinal Genome-Wide Association of Cardiovascular Disease Risk Factors in the Bogalusa Heart Study. PLoS Genet 6(9): e1001094. doi:10.1371/journal.pgen.1001094 en_US http://dx.doi.org/10.1371/journal.pgen.1001094 PLoS Genetics Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf PLoS |
| spellingShingle | Peltonen, Leena Smith, Erin N. Chen, Wei Kahonen, Mika Kettunen, Johannes Lehtimaki, Terho Raitakari, Olli T. Salem, Rany M. Schork, Nicholas J. Shaw, Marian Srinivasan, Sathanur R. Topol, Eric J. Viikari, Jorma S. Berenson, Gerald S. Murray, Sarah S. Longitudinal Genome-Wide Association of Cardiovascular Disease Risk Factors in the Bogalusa Heart Study |
| title | Longitudinal Genome-Wide Association of Cardiovascular Disease Risk Factors in the Bogalusa Heart Study |
| title_full | Longitudinal Genome-Wide Association of Cardiovascular Disease Risk Factors in the Bogalusa Heart Study |
| title_fullStr | Longitudinal Genome-Wide Association of Cardiovascular Disease Risk Factors in the Bogalusa Heart Study |
| title_full_unstemmed | Longitudinal Genome-Wide Association of Cardiovascular Disease Risk Factors in the Bogalusa Heart Study |
| title_short | Longitudinal Genome-Wide Association of Cardiovascular Disease Risk Factors in the Bogalusa Heart Study |
| title_sort | longitudinal genome wide association of cardiovascular disease risk factors in the bogalusa heart study |
| url | http://hdl.handle.net/1721.1/60304 |
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