A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies

Ariel Brautbar; Lisa A. Pompeii; Abbas Dehghan; Julius S. Ngwa; Vijay Nambi; Salim S. Virani; Fernando Rivadeneira; André G. Uitterlinden; Albert Hofman; Jacqueline C M Witteman; Michael J. Pencina; Aaron R. Folsom; L. Adrienne Cupples; Christie M. Ballantyne; Eric Boerwinkle

doi:10.1016/j.atherosclerosis.2012.05.035

A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies

Ariel Brautbar, Lisa A. Pompeii, Abbas Dehghan, Julius S. Ngwa, Vijay Nambi, Salim S. Virani, Fernando Rivadeneira, André G. Uitterlinden, Albert Hofman, Jacqueline C M Witteman, Michael J. Pencina, Aaron R. Folsom, L. Adrienne Cupples, Christie M. Ballantyne, Eric Boerwinkle

Epidemiology & Community Health

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

60 Scopus citations

Abstract

Objective: Multiple studies have identified single-nucleotide polymorphisms (SNPs) that are associated with coronary heart disease (CHD). We examined whether SNPs selected based on predefined criteria will improve CHD risk prediction when added to traditional risk factors (TRFs). Methods: SNPs were selected from the literature based on association with CHD, lack of association with a known CHD risk factor, and successful replication. A genetic risk score (GRS) was constructed based on these SNPs. Cox proportional hazards model was used to calculate CHD risk based on the Atherosclerosis Risk in Communities (ARIC) and Framingham CHD risk scores with and without the GRS. Results: The GRS was associated with risk for CHD (hazard ratio [HR] = 1.10; 95% confidence interval [CI]: 1.07-1.13). Addition of the GRS to the ARIC risk score significantly improved discrimination, reclassification, and calibration beyond that afforded by TRFs alone in non-Hispanic whites in the ARIC study. The area under the receiver operating characteristic curve (AUC) increased from 0.742 to 0.749 (Δ = 0.007; 95% CI, 0.004-0.013), and the net reclassification index (NRI) was 6.3%. Although the risk estimates for CHD in the Framingham Offspring (HR = 1.12; 95% CI: 1.10-1.14) and Rotterdam (HR = 1.08; 95% CI: 1.02-1.14) Studies were significantly improved by adding the GRS to TRFs, improvements in AUC and NRI were modest. Conclusion: Addition of a GRS based on direct associations with CHD to TRFs significantly improved discrimination and reclassification in white participants of the ARIC Study, with no significant improvement in the Rotterdam and Framingham Offspring Studies.

Original language	English (US)
Pages (from-to)	421-426
Number of pages	6
Journal	Atherosclerosis
Volume	223
Issue number	2
DOIs	https://doi.org/10.1016/j.atherosclerosis.2012.05.035
State	Published - Aug 2012

Bibliographical note

Funding Information:
The ARIC 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 NIH contract HHSN268200625226C . Infrastructure was partly supported by grant UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. Genotyping was funded by the Netherlands Organisation of Scientific Research NWO Investments (175.010.2005.011, 911-03–012), the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) project nr. 050-060-810. Abbas Dehghan is supported by NWO grant (Vici, 918-76–619). Dr Brautbar is supported by NIH grant 1P30HL101255-01. The Framingham Heart Study of the National Heart, Lung, and Blood Institute of the NIH and Boston University School of Medicine is supported by NIH contract N01–HC–25195.

Keywords

Coronary disease
Genetics
Risk factors

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Brautbar, A., Pompeii, L. A., Dehghan, A., Ngwa, J. S., Nambi, V., Virani, S. S., Rivadeneira, F., Uitterlinden, A. G., Hofman, A., Witteman, J. C. M., Pencina, M. J., Folsom, A. R., Cupples, L. A., Ballantyne, C. M., & Boerwinkle, E. (2012). A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies. Atherosclerosis, 223(2), 421-426. https://doi.org/10.1016/j.atherosclerosis.2012.05.035

A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies. / Brautbar, Ariel; Pompeii, Lisa A.; Dehghan, Abbas et al.
In: Atherosclerosis, Vol. 223, No. 2, 08.2012, p. 421-426.

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

Brautbar, A, Pompeii, LA, Dehghan, A, Ngwa, JS, Nambi, V, Virani, SS, Rivadeneira, F, Uitterlinden, AG, Hofman, A, Witteman, JCM, Pencina, MJ, Folsom, AR, Cupples, LA, Ballantyne, CM & Boerwinkle, E 2012, 'A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies', Atherosclerosis, vol. 223, no. 2, pp. 421-426. https://doi.org/10.1016/j.atherosclerosis.2012.05.035

Brautbar A, Pompeii LA, Dehghan A, Ngwa JS, Nambi V, Virani SS et al. A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies. Atherosclerosis. 2012 Aug;223(2):421-426. doi: 10.1016/j.atherosclerosis.2012.05.035

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title = "A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies",

abstract = "Objective: Multiple studies have identified single-nucleotide polymorphisms (SNPs) that are associated with coronary heart disease (CHD). We examined whether SNPs selected based on predefined criteria will improve CHD risk prediction when added to traditional risk factors (TRFs). Methods: SNPs were selected from the literature based on association with CHD, lack of association with a known CHD risk factor, and successful replication. A genetic risk score (GRS) was constructed based on these SNPs. Cox proportional hazards model was used to calculate CHD risk based on the Atherosclerosis Risk in Communities (ARIC) and Framingham CHD risk scores with and without the GRS. Results: The GRS was associated with risk for CHD (hazard ratio [HR] = 1.10; 95% confidence interval [CI]: 1.07-1.13). Addition of the GRS to the ARIC risk score significantly improved discrimination, reclassification, and calibration beyond that afforded by TRFs alone in non-Hispanic whites in the ARIC study. The area under the receiver operating characteristic curve (AUC) increased from 0.742 to 0.749 (Δ = 0.007; 95% CI, 0.004-0.013), and the net reclassification index (NRI) was 6.3%. Although the risk estimates for CHD in the Framingham Offspring (HR = 1.12; 95% CI: 1.10-1.14) and Rotterdam (HR = 1.08; 95% CI: 1.02-1.14) Studies were significantly improved by adding the GRS to TRFs, improvements in AUC and NRI were modest. Conclusion: Addition of a GRS based on direct associations with CHD to TRFs significantly improved discrimination and reclassification in white participants of the ARIC Study, with no significant improvement in the Rotterdam and Framingham Offspring Studies.",

keywords = "Coronary disease, Genetics, Risk factors",

author = "Ariel Brautbar and Pompeii, {Lisa A.} and Abbas Dehghan and Ngwa, {Julius S.} and Vijay Nambi and Virani, {Salim S.} and Fernando Rivadeneira and Uitterlinden, {Andr{\'e} G.} and Albert Hofman and Witteman, {Jacqueline C M} and Pencina, {Michael J.} and Folsom, {Aaron R.} and Cupples, {L. Adrienne} and Ballantyne, {Christie M.} and Eric Boerwinkle",

note = "Funding Information: The ARIC 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 NIH contract HHSN268200625226C . Infrastructure was partly supported by grant UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. Genotyping was funded by the Netherlands Organisation of Scientific Research NWO Investments (175.010.2005.011, 911-03–012), the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) project nr. 050-060-810. Abbas Dehghan is supported by NWO grant (Vici, 918-76–619). Dr Brautbar is supported by NIH grant 1P30HL101255-01. The Framingham Heart Study of the National Heart, Lung, and Blood Institute of the NIH and Boston University School of Medicine is supported by NIH contract N01–HC–25195. ",

year = "2012",

month = aug,

doi = "10.1016/j.atherosclerosis.2012.05.035",

language = "English (US)",

volume = "223",

pages = "421--426",

journal = "Atherosclerosis",

issn = "0021-9150",

publisher = "Elsevier Ireland Ltd",

number = "2",

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TY - JOUR

T1 - A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies

AU - Brautbar, Ariel

AU - Pompeii, Lisa A.

AU - Dehghan, Abbas

AU - Ngwa, Julius S.

AU - Nambi, Vijay

AU - Virani, Salim S.

AU - Rivadeneira, Fernando

AU - Uitterlinden, André G.

AU - Hofman, Albert

AU - Witteman, Jacqueline C M

AU - Pencina, Michael J.

AU - Folsom, Aaron R.

AU - Cupples, L. Adrienne

AU - Ballantyne, Christie M.

AU - Boerwinkle, Eric

N1 - Funding Information: The ARIC 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 NIH contract HHSN268200625226C . Infrastructure was partly supported by grant UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. Genotyping was funded by the Netherlands Organisation of Scientific Research NWO Investments (175.010.2005.011, 911-03–012), the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) project nr. 050-060-810. Abbas Dehghan is supported by NWO grant (Vici, 918-76–619). Dr Brautbar is supported by NIH grant 1P30HL101255-01. The Framingham Heart Study of the National Heart, Lung, and Blood Institute of the NIH and Boston University School of Medicine is supported by NIH contract N01–HC–25195.

PY - 2012/8

Y1 - 2012/8

N2 - Objective: Multiple studies have identified single-nucleotide polymorphisms (SNPs) that are associated with coronary heart disease (CHD). We examined whether SNPs selected based on predefined criteria will improve CHD risk prediction when added to traditional risk factors (TRFs). Methods: SNPs were selected from the literature based on association with CHD, lack of association with a known CHD risk factor, and successful replication. A genetic risk score (GRS) was constructed based on these SNPs. Cox proportional hazards model was used to calculate CHD risk based on the Atherosclerosis Risk in Communities (ARIC) and Framingham CHD risk scores with and without the GRS. Results: The GRS was associated with risk for CHD (hazard ratio [HR] = 1.10; 95% confidence interval [CI]: 1.07-1.13). Addition of the GRS to the ARIC risk score significantly improved discrimination, reclassification, and calibration beyond that afforded by TRFs alone in non-Hispanic whites in the ARIC study. The area under the receiver operating characteristic curve (AUC) increased from 0.742 to 0.749 (Δ = 0.007; 95% CI, 0.004-0.013), and the net reclassification index (NRI) was 6.3%. Although the risk estimates for CHD in the Framingham Offspring (HR = 1.12; 95% CI: 1.10-1.14) and Rotterdam (HR = 1.08; 95% CI: 1.02-1.14) Studies were significantly improved by adding the GRS to TRFs, improvements in AUC and NRI were modest. Conclusion: Addition of a GRS based on direct associations with CHD to TRFs significantly improved discrimination and reclassification in white participants of the ARIC Study, with no significant improvement in the Rotterdam and Framingham Offspring Studies.

AB - Objective: Multiple studies have identified single-nucleotide polymorphisms (SNPs) that are associated with coronary heart disease (CHD). We examined whether SNPs selected based on predefined criteria will improve CHD risk prediction when added to traditional risk factors (TRFs). Methods: SNPs were selected from the literature based on association with CHD, lack of association with a known CHD risk factor, and successful replication. A genetic risk score (GRS) was constructed based on these SNPs. Cox proportional hazards model was used to calculate CHD risk based on the Atherosclerosis Risk in Communities (ARIC) and Framingham CHD risk scores with and without the GRS. Results: The GRS was associated with risk for CHD (hazard ratio [HR] = 1.10; 95% confidence interval [CI]: 1.07-1.13). Addition of the GRS to the ARIC risk score significantly improved discrimination, reclassification, and calibration beyond that afforded by TRFs alone in non-Hispanic whites in the ARIC study. The area under the receiver operating characteristic curve (AUC) increased from 0.742 to 0.749 (Δ = 0.007; 95% CI, 0.004-0.013), and the net reclassification index (NRI) was 6.3%. Although the risk estimates for CHD in the Framingham Offspring (HR = 1.12; 95% CI: 1.10-1.14) and Rotterdam (HR = 1.08; 95% CI: 1.02-1.14) Studies were significantly improved by adding the GRS to TRFs, improvements in AUC and NRI were modest. Conclusion: Addition of a GRS based on direct associations with CHD to TRFs significantly improved discrimination and reclassification in white participants of the ARIC Study, with no significant improvement in the Rotterdam and Framingham Offspring Studies.

KW - Coronary disease

KW - Genetics

KW - Risk factors

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ER -

A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies

Abstract

Bibliographical note

Keywords

UN SDGs

Publisher link

Find It

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