Hypertension genetic risk score is associated with burden of coronary heart disease among patients referred for coronary angiography

Maria Lukacs Krogager; Regitze Kuhr Skals; Emil Vincent R. Appel; Theresia Maria Schnurr; Line Engelbrechtsen; Christian Theil Have; Oluf Borbye Pedersen; Thomas Engstrøm; Dan M. Roden; Gunnar Gislason; Henrik Enghusen Poulsen; Lars Køber; Steen Stender; Torben Hansen; Niels Grarup; Charlotte Andersson; Christian Torp-Pedersen; Peter E. Weeke

doi:10.1371/journal.pone.0208645

Hypertension genetic risk score is associated with burden of coronary heart disease among patients referred for coronary angiography

Maria Lukacs Krogager, Regitze Kuhr Skals, Emil Vincent R. Appel, Theresia Maria Schnurr, Line Engelbrechtsen, Christian Theil Have, Oluf Borbye Pedersen, Thomas Engstrøm, Dan M. Roden, Gunnar Gislason, Henrik Enghusen Poulsen, Lars Køber, Steen Stender, Torben Hansen, Niels Grarup, Charlotte Andersson, Christian Torp-Pedersen, Peter E. Weeke

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Abstract

Background Recent GWAS studies have identified more than 300 SNPs associated with variation in blood pressure. We investigated whether a genetic risk score constructed from these variants is associated with burden of coronary heart disease. Methods From 2010–2014, 4,809 individuals admitted to coronary angiography in Capital Region of Copenhagen were genotyped. We calculated hypertension GRS comprised of GWAS identified SNPs associated with blood pressure. We performed logistic regression analyses to estimate the risk of hypertension and prevalent CHD. We also assessed the severity of CHD associated with the GRS. The analyses were performed using GRS quartiles. We used the Inter99 cohort to validate our results and to investigate for possible pleiotropy for the GRS with other CHD risk factors. Results In COGEN, adjusted odds ratios comparing the 2^nd, 3^rd and 4^th cumulative GRS quartiles with the reference were 1.12(95% CI 0.95–1.33), 1.35(95% CI 1.14–1.59) and 1.29(95% CI 1.09–1.53) respectively, for prevalent CHD. The adjusted multinomial logistic regression showed that 3^rd and 4^th GRS quartiles were associated with increased odds of developing two(OR 1.33, 95% CI 1.04–1.71 and OR 1.36, 95% CI 1.06–1.75, respectively) and three coronary vessel disease(OR 1.77, 95% CI 1.36–2.30 and OR 1.65, 95% CI 1.26–2.15, respectively). Similar results for incident CHD were observed in the Inter99 cohort. The hypertension GRS did not associate with type 2 diabetes, smoking, BMI or hyperlipidemia. Conclusion Hypertension GRS quartiles were associated with an increased risk of hypertension, prevalent CHD, and burden of coronary vessel disease in a dose-response pattern. We showed no evidence for pleiotropy with other risk factors for CHD.

Original language	English
Article number	e0208645
Journal	P L o S One
Volume	13
Issue number	12
Pages (from-to)	1-17
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0208645
Publication status	Published - 1 Jul 2019

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Hypertension genetic risk score is associated with burden of coronary heart disease among patients referred for coronary angiographyFinal published version, 1.01 MB

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Krogager, M. L., Skals, R. K., Appel, E. V. R., Schnurr, T. M., Engelbrechtsen, L., Have, C. T., Pedersen, O. B., Engstrøm, T., Roden, D. M., Gislason, G., Poulsen, H. E., Køber, L., Stender, S., Hansen, T., Grarup, N., Andersson, C., Torp-Pedersen, C., & Weeke, P. E. (2019). Hypertension genetic risk score is associated with burden of coronary heart disease among patients referred for coronary angiography. P L o S One, 13(12), 1-17. [e0208645]. https://doi.org/10.1371/journal.pone.0208645

Krogager, ML, Skals, RK, Appel, EVR, Schnurr, TM, Engelbrechtsen, L, Have, CT, Pedersen, OB , Engstrøm, T, Roden, DM, Gislason, G , Poulsen, HE , Køber, L , Stender, S , Hansen, T , Grarup, N, Andersson, C, Torp-Pedersen, C & Weeke, PE 2019, 'Hypertension genetic risk score is associated with burden of coronary heart disease among patients referred for coronary angiography', P L o S One, vol. 13, no. 12, e0208645, pp. 1-17. https://doi.org/10.1371/journal.pone.0208645

@article{04339761bfa741eab083ffe212e0a894,

title = "Hypertension genetic risk score is associated with burden of coronary heart disease among patients referred for coronary angiography",

abstract = "Background Recent GWAS studies have identified more than 300 SNPs associated with variation in blood pressure. We investigated whether a genetic risk score constructed from these variants is associated with burden of coronary heart disease. Methods From 2010–2014, 4,809 individuals admitted to coronary angiography in Capital Region of Copenhagen were genotyped. We calculated hypertension GRS comprised of GWAS identified SNPs associated with blood pressure. We performed logistic regression analyses to estimate the risk of hypertension and prevalent CHD. We also assessed the severity of CHD associated with the GRS. The analyses were performed using GRS quartiles. We used the Inter99 cohort to validate our results and to investigate for possible pleiotropy for the GRS with other CHD risk factors. Results In COGEN, adjusted odds ratios comparing the 2nd, 3rd and 4th cumulative GRS quartiles with the reference were 1.12(95% CI 0.95–1.33), 1.35(95% CI 1.14–1.59) and 1.29(95% CI 1.09–1.53) respectively, for prevalent CHD. The adjusted multinomial logistic regression showed that 3rd and 4th GRS quartiles were associated with increased odds of developing two(OR 1.33, 95% CI 1.04–1.71 and OR 1.36, 95% CI 1.06–1.75, respectively) and three coronary vessel disease(OR 1.77, 95% CI 1.36–2.30 and OR 1.65, 95% CI 1.26–2.15, respectively). Similar results for incident CHD were observed in the Inter99 cohort. The hypertension GRS did not associate with type 2 diabetes, smoking, BMI or hyperlipidemia. Conclusion Hypertension GRS quartiles were associated with an increased risk of hypertension, prevalent CHD, and burden of coronary vessel disease in a dose-response pattern. We showed no evidence for pleiotropy with other risk factors for CHD.",

author = "Krogager, {Maria Lukacs} and Skals, {Regitze Kuhr} and Appel, {Emil Vincent R.} and Schnurr, {Theresia Maria} and Line Engelbrechtsen and Have, {Christian Theil} and Pedersen, {Oluf Borbye} and Thomas Engstr{\o}m and Roden, {Dan M.} and Gunnar Gislason and Poulsen, {Henrik Enghusen} and Lars K{\o}ber and Steen Stender and Torben Hansen and Niels Grarup and Charlotte Andersson and Christian Torp-Pedersen and Weeke, {Peter E.}",

year = "2019",

month = jul,

day = "1",

doi = "10.1371/journal.pone.0208645",

language = "English",

volume = "13",

pages = "1--17",

journal = "PLoS Computational Biology",

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TY - JOUR

T1 - Hypertension genetic risk score is associated with burden of coronary heart disease among patients referred for coronary angiography

AU - Krogager, Maria Lukacs

AU - Skals, Regitze Kuhr

AU - Appel, Emil Vincent R.

AU - Schnurr, Theresia Maria

AU - Engelbrechtsen, Line

AU - Have, Christian Theil

AU - Pedersen, Oluf Borbye

AU - Engstrøm, Thomas

AU - Roden, Dan M.

AU - Gislason, Gunnar

AU - Poulsen, Henrik Enghusen

AU - Køber, Lars

AU - Stender, Steen

AU - Hansen, Torben

AU - Grarup, Niels

AU - Andersson, Charlotte

AU - Torp-Pedersen, Christian

AU - Weeke, Peter E.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Background Recent GWAS studies have identified more than 300 SNPs associated with variation in blood pressure. We investigated whether a genetic risk score constructed from these variants is associated with burden of coronary heart disease. Methods From 2010–2014, 4,809 individuals admitted to coronary angiography in Capital Region of Copenhagen were genotyped. We calculated hypertension GRS comprised of GWAS identified SNPs associated with blood pressure. We performed logistic regression analyses to estimate the risk of hypertension and prevalent CHD. We also assessed the severity of CHD associated with the GRS. The analyses were performed using GRS quartiles. We used the Inter99 cohort to validate our results and to investigate for possible pleiotropy for the GRS with other CHD risk factors. Results In COGEN, adjusted odds ratios comparing the 2nd, 3rd and 4th cumulative GRS quartiles with the reference were 1.12(95% CI 0.95–1.33), 1.35(95% CI 1.14–1.59) and 1.29(95% CI 1.09–1.53) respectively, for prevalent CHD. The adjusted multinomial logistic regression showed that 3rd and 4th GRS quartiles were associated with increased odds of developing two(OR 1.33, 95% CI 1.04–1.71 and OR 1.36, 95% CI 1.06–1.75, respectively) and three coronary vessel disease(OR 1.77, 95% CI 1.36–2.30 and OR 1.65, 95% CI 1.26–2.15, respectively). Similar results for incident CHD were observed in the Inter99 cohort. The hypertension GRS did not associate with type 2 diabetes, smoking, BMI or hyperlipidemia. Conclusion Hypertension GRS quartiles were associated with an increased risk of hypertension, prevalent CHD, and burden of coronary vessel disease in a dose-response pattern. We showed no evidence for pleiotropy with other risk factors for CHD.

AB - Background Recent GWAS studies have identified more than 300 SNPs associated with variation in blood pressure. We investigated whether a genetic risk score constructed from these variants is associated with burden of coronary heart disease. Methods From 2010–2014, 4,809 individuals admitted to coronary angiography in Capital Region of Copenhagen were genotyped. We calculated hypertension GRS comprised of GWAS identified SNPs associated with blood pressure. We performed logistic regression analyses to estimate the risk of hypertension and prevalent CHD. We also assessed the severity of CHD associated with the GRS. The analyses were performed using GRS quartiles. We used the Inter99 cohort to validate our results and to investigate for possible pleiotropy for the GRS with other CHD risk factors. Results In COGEN, adjusted odds ratios comparing the 2nd, 3rd and 4th cumulative GRS quartiles with the reference were 1.12(95% CI 0.95–1.33), 1.35(95% CI 1.14–1.59) and 1.29(95% CI 1.09–1.53) respectively, for prevalent CHD. The adjusted multinomial logistic regression showed that 3rd and 4th GRS quartiles were associated with increased odds of developing two(OR 1.33, 95% CI 1.04–1.71 and OR 1.36, 95% CI 1.06–1.75, respectively) and three coronary vessel disease(OR 1.77, 95% CI 1.36–2.30 and OR 1.65, 95% CI 1.26–2.15, respectively). Similar results for incident CHD were observed in the Inter99 cohort. The hypertension GRS did not associate with type 2 diabetes, smoking, BMI or hyperlipidemia. Conclusion Hypertension GRS quartiles were associated with an increased risk of hypertension, prevalent CHD, and burden of coronary vessel disease in a dose-response pattern. We showed no evidence for pleiotropy with other risk factors for CHD.

U2 - 10.1371/journal.pone.0208645

DO - 10.1371/journal.pone.0208645

M3 - Journal article

C2 - 30566436

SN - 1932-6203

VL - 13

SP - 1

EP - 17

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 12

M1 - e0208645

ER -

Hypertension genetic risk score is associated with burden of coronary heart disease among patients referred for coronary angiography

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