Genetic loci associated with ideal cardiovascular health: A meta-analysis of genome-wide association studies

Norrina B. Allen; Donald Lloyd-Jones; Shih Jen Hwang; Laura Rasmussen-Torvik; Myriam Fornage; Alanna C. Morrison; Abigail S. Baldridge; Eric Boerwinkle; Daniel Levy; L. Adrienne Cupples; Caroline S. Fox; George Thanassoulis; Line Dufresne; Martha Daviglus; Andrew D. Johnson; Jared Reis; Jerome Rotter; Walter Palmas; Mathew Allison; James S. Pankow; Christopher J. O'Donnell

doi:10.1016/j.ahj.2015.12.022

Genetic loci associated with ideal cardiovascular health: A meta-analysis of genome-wide association studies

Norrina B. Allen, Donald Lloyd-Jones, Shih Jen Hwang, Laura Rasmussen-Torvik, Myriam Fornage, Alanna C. Morrison, Abigail S. Baldridge, Eric Boerwinkle, Daniel Levy, L. Adrienne Cupples, Caroline S. Fox, George Thanassoulis, Line Dufresne, Martha Daviglus, Andrew D. Johnson, Jared Reis, Jerome Rotter, Walter Palmas, Mathew Allison, James S. PankowChristopher J. O'Donnell

Epidemiology

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

Background Multiple genetic loci are associated with clinical cardiovascular (CV) disease and individual CV risk factors. Individuals with ideal levels of all major CV risk factors have very low risk for CV disease morbidity or mortality. Ideal levels of risk factors can be attained by lifestyle modifications; however, little is known about gene variants associated with ideal CV health. Our objective was to carry out a genome-wide association study on the trait. Methods and Results We examined 2 dichotomous phenotypes of ideal CV health - clinical (untreated cholesterol <200 mg/dL, untreated blood pressure <120/<80, not diabetic) and clinical + behavioral (clinical plus: not a current smoker, body mass index <25 kg/m²) - among white participants aged 50 ± 5 years. We performed a meta-analysis of 4 genome-wide association studies (total n = 11,708) from the MESA, CARDIA, ARIC, and Framingham Heart Study cohorts. We identified a single-nucleotide polymorphism (rs445925) in the APOC1/APOE region that was associated with clinical ideal CV health at genome-wide level of significance (P < 2.0 × 10^-9). The significance of this region was validated using exome chip genotyping. The association with ideal CV health was attenuated after adjusting for low-density lipoprotein cholesterol. Conclusion A common single-nucleotide polymorphism in the APOC1/APOE region, previously found to be associated with protective levels of cholesterol and lower CV risk, may be associated with ideal health. In future replication studies, larger sample sizes may be needed to detect loci with more modest effects on ideal CV health. In addition to the important impact of lifestyle modifications, we have identified evidence for gene variation that plays a role in ideal CV health.

Original language	English (US)
Pages (from-to)	112-120
Number of pages	9
Journal	American Heart Journal
Volume	175
DOIs	https://doi.org/10.1016/j.ahj.2015.12.022
State	Published - May 1 2016

Bibliographical note

Funding Information:
The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute Contracts ( HHSN268201100005C , HHSN268201100006C , HHSN268201100007C , HHSN268201100008C , HHSN268201100009C , HHSN268201100010C , HHSN268201100011C , and HHSN268201100012C ), R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute Contract U01HG004402 ; and National Institutes of Health Contract HHSN268200625226C . The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant No. UL1RR025005 , a component of the National Institutes of Health and NIH Roadmap for Medical Research .

Funding Information:
This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195 ).

Funding Information:
We acknowledge the important role of the Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) consortium and the collaboration of the CHARGE Subclinical Atherosclerosis/Coronary Heart Disease Working Group in the development and support of this manuscript.

Publisher Copyright:
© 2015 Mosby, Inc. All rights reserved.

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Allen, N. B., Lloyd-Jones, D., Hwang, S. J., Rasmussen-Torvik, L., Fornage, M., Morrison, A. C., Baldridge, A. S., Boerwinkle, E., Levy, D., Cupples, L. A., Fox, C. S., Thanassoulis, G., Dufresne, L., Daviglus, M., Johnson, A. D., Reis, J., Rotter, J., Palmas, W., Allison, M., ... O'Donnell, C. J. (2016). Genetic loci associated with ideal cardiovascular health: A meta-analysis of genome-wide association studies. American Heart Journal, 175, 112-120. https://doi.org/10.1016/j.ahj.2015.12.022

Allen, NB, Lloyd-Jones, D, Hwang, SJ, Rasmussen-Torvik, L, Fornage, M, Morrison, AC, Baldridge, AS, Boerwinkle, E, Levy, D, Cupples, LA, Fox, CS, Thanassoulis, G, Dufresne, L, Daviglus, M, Johnson, AD, Reis, J, Rotter, J, Palmas, W, Allison, M, Pankow, JS & O'Donnell, CJ 2016, 'Genetic loci associated with ideal cardiovascular health: A meta-analysis of genome-wide association studies', American Heart Journal, vol. 175, pp. 112-120. https://doi.org/10.1016/j.ahj.2015.12.022

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title = "Genetic loci associated with ideal cardiovascular health: A meta-analysis of genome-wide association studies",

abstract = "Background Multiple genetic loci are associated with clinical cardiovascular (CV) disease and individual CV risk factors. Individuals with ideal levels of all major CV risk factors have very low risk for CV disease morbidity or mortality. Ideal levels of risk factors can be attained by lifestyle modifications; however, little is known about gene variants associated with ideal CV health. Our objective was to carry out a genome-wide association study on the trait. Methods and Results We examined 2 dichotomous phenotypes of ideal CV health - clinical (untreated cholesterol <200 mg/dL, untreated blood pressure <120/<80, not diabetic) and clinical + behavioral (clinical plus: not a current smoker, body mass index <25 kg/m2) - among white participants aged 50 ± 5 years. We performed a meta-analysis of 4 genome-wide association studies (total n = 11,708) from the MESA, CARDIA, ARIC, and Framingham Heart Study cohorts. We identified a single-nucleotide polymorphism (rs445925) in the APOC1/APOE region that was associated with clinical ideal CV health at genome-wide level of significance (P < 2.0 × 10-9). The significance of this region was validated using exome chip genotyping. The association with ideal CV health was attenuated after adjusting for low-density lipoprotein cholesterol. Conclusion A common single-nucleotide polymorphism in the APOC1/APOE region, previously found to be associated with protective levels of cholesterol and lower CV risk, may be associated with ideal health. In future replication studies, larger sample sizes may be needed to detect loci with more modest effects on ideal CV health. In addition to the important impact of lifestyle modifications, we have identified evidence for gene variation that plays a role in ideal CV health.",

author = "Allen, {Norrina B.} and Donald Lloyd-Jones and Hwang, {Shih Jen} and Laura Rasmussen-Torvik and Myriam Fornage and Morrison, {Alanna C.} and Baldridge, {Abigail S.} and Eric Boerwinkle and Daniel Levy and Cupples, {L. Adrienne} and Fox, {Caroline S.} and George Thanassoulis and Line Dufresne and Martha Daviglus and Johnson, {Andrew D.} and Jared Reis and Jerome Rotter and Walter Palmas and Mathew Allison and Pankow, {James S.} and O'Donnell, {Christopher J.}",

note = "Funding Information: The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute Contracts ( HHSN268201100005C , HHSN268201100006C , HHSN268201100007C , HHSN268201100008C , HHSN268201100009C , HHSN268201100010C , HHSN268201100011C , and HHSN268201100012C ), R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute Contract U01HG004402 ; and National Institutes of Health Contract HHSN268200625226C . The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant No. UL1RR025005 , a component of the National Institutes of Health and NIH Roadmap for Medical Research . Funding Information: This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195 ). Funding Information: We acknowledge the important role of the Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) consortium and the collaboration of the CHARGE Subclinical Atherosclerosis/Coronary Heart Disease Working Group in the development and support of this manuscript. Publisher Copyright: {\textcopyright} 2015 Mosby, Inc. All rights reserved.",

year = "2016",

month = may,

day = "1",

doi = "10.1016/j.ahj.2015.12.022",

language = "English (US)",

volume = "175",

pages = "112--120",

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TY - JOUR

T1 - Genetic loci associated with ideal cardiovascular health

T2 - A meta-analysis of genome-wide association studies

AU - Allen, Norrina B.

AU - Lloyd-Jones, Donald

AU - Hwang, Shih Jen

AU - Rasmussen-Torvik, Laura

AU - Fornage, Myriam

AU - Morrison, Alanna C.

AU - Baldridge, Abigail S.

AU - Boerwinkle, Eric

AU - Levy, Daniel

AU - Cupples, L. Adrienne

AU - Fox, Caroline S.

AU - Thanassoulis, George

AU - Dufresne, Line

AU - Daviglus, Martha

AU - Johnson, Andrew D.

AU - Reis, Jared

AU - Rotter, Jerome

AU - Palmas, Walter

AU - Allison, Mathew

AU - Pankow, James S.

AU - O'Donnell, Christopher J.

N1 - Funding Information: The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute Contracts ( HHSN268201100005C , HHSN268201100006C , HHSN268201100007C , HHSN268201100008C , HHSN268201100009C , HHSN268201100010C , HHSN268201100011C , and HHSN268201100012C ), R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute Contract U01HG004402 ; and National Institutes of Health Contract HHSN268200625226C . The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant No. UL1RR025005 , a component of the National Institutes of Health and NIH Roadmap for Medical Research . Funding Information: This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195 ). Funding Information: We acknowledge the important role of the Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) consortium and the collaboration of the CHARGE Subclinical Atherosclerosis/Coronary Heart Disease Working Group in the development and support of this manuscript. Publisher Copyright: © 2015 Mosby, Inc. All rights reserved.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Background Multiple genetic loci are associated with clinical cardiovascular (CV) disease and individual CV risk factors. Individuals with ideal levels of all major CV risk factors have very low risk for CV disease morbidity or mortality. Ideal levels of risk factors can be attained by lifestyle modifications; however, little is known about gene variants associated with ideal CV health. Our objective was to carry out a genome-wide association study on the trait. Methods and Results We examined 2 dichotomous phenotypes of ideal CV health - clinical (untreated cholesterol <200 mg/dL, untreated blood pressure <120/<80, not diabetic) and clinical + behavioral (clinical plus: not a current smoker, body mass index <25 kg/m2) - among white participants aged 50 ± 5 years. We performed a meta-analysis of 4 genome-wide association studies (total n = 11,708) from the MESA, CARDIA, ARIC, and Framingham Heart Study cohorts. We identified a single-nucleotide polymorphism (rs445925) in the APOC1/APOE region that was associated with clinical ideal CV health at genome-wide level of significance (P < 2.0 × 10-9). The significance of this region was validated using exome chip genotyping. The association with ideal CV health was attenuated after adjusting for low-density lipoprotein cholesterol. Conclusion A common single-nucleotide polymorphism in the APOC1/APOE region, previously found to be associated with protective levels of cholesterol and lower CV risk, may be associated with ideal health. In future replication studies, larger sample sizes may be needed to detect loci with more modest effects on ideal CV health. In addition to the important impact of lifestyle modifications, we have identified evidence for gene variation that plays a role in ideal CV health.

AB - Background Multiple genetic loci are associated with clinical cardiovascular (CV) disease and individual CV risk factors. Individuals with ideal levels of all major CV risk factors have very low risk for CV disease morbidity or mortality. Ideal levels of risk factors can be attained by lifestyle modifications; however, little is known about gene variants associated with ideal CV health. Our objective was to carry out a genome-wide association study on the trait. Methods and Results We examined 2 dichotomous phenotypes of ideal CV health - clinical (untreated cholesterol <200 mg/dL, untreated blood pressure <120/<80, not diabetic) and clinical + behavioral (clinical plus: not a current smoker, body mass index <25 kg/m2) - among white participants aged 50 ± 5 years. We performed a meta-analysis of 4 genome-wide association studies (total n = 11,708) from the MESA, CARDIA, ARIC, and Framingham Heart Study cohorts. We identified a single-nucleotide polymorphism (rs445925) in the APOC1/APOE region that was associated with clinical ideal CV health at genome-wide level of significance (P < 2.0 × 10-9). The significance of this region was validated using exome chip genotyping. The association with ideal CV health was attenuated after adjusting for low-density lipoprotein cholesterol. Conclusion A common single-nucleotide polymorphism in the APOC1/APOE region, previously found to be associated with protective levels of cholesterol and lower CV risk, may be associated with ideal health. In future replication studies, larger sample sizes may be needed to detect loci with more modest effects on ideal CV health. In addition to the important impact of lifestyle modifications, we have identified evidence for gene variation that plays a role in ideal CV health.

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Genetic loci associated with ideal cardiovascular health: A meta-analysis of genome-wide association studies

Abstract

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