TY - JOUR
T1 - Hypertension genetic risk score is associated with burden of coronary heart disease among patients referred for coronary angiography
AU - Lukács Krogager, Maria
AU - Skals, Regitze Kuhr
AU - Appel, Emil Vincent R
AU - Schnurr, Theresia M
AU - Engelbrechtsen, Line
AU - Have, Christian Theil
AU - Pedersen, Oluf
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 - 2018/1/1
Y1 - 2018/1/1
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.
UR - http://www.scopus.com/inward/record.url?scp=85058837355&partnerID=8YFLogxK
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 ONE
JF - PLOS ONE
IS - 12
M1 - e0208645
ER -