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A blood pressure genetic risk score is a significant predictor of incident cardiovascular events in 32 699 individuals

A blood pressure genetic risk score is a significant predictor of incident cardiovascular events in 32 699 individuals
A blood pressure genetic risk score is a significant predictor of incident cardiovascular events in 32 699 individuals
Recent genome-wide association studies have identified genetic variants associated with blood pressure (BP). We investigated whether genetic risk scores (GRSs) constructed of these variants would predict incident cardiovascular disease (CVD) events. We genotyped 32 common single nucleotide polymorphisms in several Finnish cohorts, with up to 32 669 individuals after exclusion of prevalent CVD cases. The median follow-up was 9.8 years, during which 2295 incident CVD events occurred. We created GRSs separately for systolic BP and diastolic BP by multiplying the risk allele count of each single nucleotide polymorphism by the effect size estimated in published genome-wide association studies. We performed Cox regression analyses with and without adjustment for clinical factors, including BP at baseline in each cohort. The results were combined by inverse variance–weighted fixed-effects meta-analysis. The GRSs were strongly associated with systolic BP and diastolic BP, and baseline hypertension (all P<10?62). Hazard ratios comparing the highest quintiles of systolic BP and diastolic BP GRSs with the lowest quintiles after adjustment for age, age squared, and sex were 1.25 (1.07–1.46; P=0.006) and 1.23 (1.05–1.43; P=0.01), respectively, for incident coronary heart disease; 1.24 (1.01–1.53; P=0.04) and 1.35 (1.09–1.66; P=0.005), respectively, for incident stroke; and 1.23 (1.08–1.40; P=2×10?6) and 1.26 (1.11–1.44; P=5×10?4), respectively, for composite CVD. In conclusion, BP findings from genome-wide association studies are strongly replicated. GRSs comprising bona fide BP-single nucleotide polymorphisms predicted CVD risk, consistent with a lifelong effect on BP of these variants collectively.

blood pressure, cardiovascular disease, genetic risk score, genetics, hypertension, prospective cohort study
0194-911X
987-994
Havulinna, A.S.
76fe8f13-4003-4780-a4bb-a6d1a131c447
Kettunen, J.
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Ukkola, O.
ec863dca-0203-450e-a771-e87bd021f674
Osmond, C.
2677bf85-494f-4a78-adf8-580e1b8acb81
Eriksson, J.G.
eda300d2-b247-479f-95b9-f12d2c72e92b
Kesaniemi, Y.A.
f18fdfd1-3216-4462-99dc-99d46a3cbb45
Jula, A.
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Peltonen, L.
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Kontula, K.
fcb87245-3efd-4cb4-a781-ba08f17ba2fd
Salomaa, V.
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Newton-Cheh, C.
05f4772e-ed22-4f0e-b38f-33e65320eac2
Havulinna, A.S.
76fe8f13-4003-4780-a4bb-a6d1a131c447
Kettunen, J.
a1279081-a58e-4609-9b8a-c2e1a3d09b6f
Ukkola, O.
ec863dca-0203-450e-a771-e87bd021f674
Osmond, C.
2677bf85-494f-4a78-adf8-580e1b8acb81
Eriksson, J.G.
eda300d2-b247-479f-95b9-f12d2c72e92b
Kesaniemi, Y.A.
f18fdfd1-3216-4462-99dc-99d46a3cbb45
Jula, A.
cb00e706-feea-42b2-820d-cf22b002623e
Peltonen, L.
2f88af14-4d9c-4577-952b-18db54e87a17
Kontula, K.
fcb87245-3efd-4cb4-a781-ba08f17ba2fd
Salomaa, V.
8e74714e-dc70-4a6a-a0a6-cc61afc084b7
Newton-Cheh, C.
05f4772e-ed22-4f0e-b38f-33e65320eac2

Havulinna, A.S., Kettunen, J., Ukkola, O., Osmond, C., Eriksson, J.G., Kesaniemi, Y.A., Jula, A., Peltonen, L., Kontula, K., Salomaa, V. and Newton-Cheh, C. (2013) A blood pressure genetic risk score is a significant predictor of incident cardiovascular events in 32 699 individuals. Hypertension, 61 (5), 987-994. (doi:10.1161/HYPERTENSIONAHA.111.00649). (PMID:23509078)

Record type: Article

Abstract

Recent genome-wide association studies have identified genetic variants associated with blood pressure (BP). We investigated whether genetic risk scores (GRSs) constructed of these variants would predict incident cardiovascular disease (CVD) events. We genotyped 32 common single nucleotide polymorphisms in several Finnish cohorts, with up to 32 669 individuals after exclusion of prevalent CVD cases. The median follow-up was 9.8 years, during which 2295 incident CVD events occurred. We created GRSs separately for systolic BP and diastolic BP by multiplying the risk allele count of each single nucleotide polymorphism by the effect size estimated in published genome-wide association studies. We performed Cox regression analyses with and without adjustment for clinical factors, including BP at baseline in each cohort. The results were combined by inverse variance–weighted fixed-effects meta-analysis. The GRSs were strongly associated with systolic BP and diastolic BP, and baseline hypertension (all P<10?62). Hazard ratios comparing the highest quintiles of systolic BP and diastolic BP GRSs with the lowest quintiles after adjustment for age, age squared, and sex were 1.25 (1.07–1.46; P=0.006) and 1.23 (1.05–1.43; P=0.01), respectively, for incident coronary heart disease; 1.24 (1.01–1.53; P=0.04) and 1.35 (1.09–1.66; P=0.005), respectively, for incident stroke; and 1.23 (1.08–1.40; P=2×10?6) and 1.26 (1.11–1.44; P=5×10?4), respectively, for composite CVD. In conclusion, BP findings from genome-wide association studies are strongly replicated. GRSs comprising bona fide BP-single nucleotide polymorphisms predicted CVD risk, consistent with a lifelong effect on BP of these variants collectively.

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Published date: May 2013
Keywords: blood pressure, cardiovascular disease, genetic risk score, genetics, hypertension, prospective cohort study
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 352672
URI: http://eprints.soton.ac.uk/id/eprint/352672
ISSN: 0194-911X
PURE UUID: b84f474b-615b-4ab8-ac04-f4dfb2209beb
ORCID for C. Osmond: ORCID iD orcid.org/0000-0002-9054-4655

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Date deposited: 20 May 2013 09:33
Last modified: 18 Feb 2021 16:45

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Contributors

Author: A.S. Havulinna
Author: J. Kettunen
Author: O. Ukkola
Author: C. Osmond ORCID iD
Author: J.G. Eriksson
Author: Y.A. Kesaniemi
Author: A. Jula
Author: L. Peltonen
Author: K. Kontula
Author: V. Salomaa
Author: C. Newton-Cheh

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