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Risk prediction by genetic risk scores for coronary heart disease is independent of self-reported family history

AIMS: Genetic risk scores (GRSs) have been associated with coronary heart disease (CHD) in large studies. We asked whether expanding an established 27-variant GRS (GRS27) to a 50-variant GRS (GRS50) improved CHD prediction and whether GRSs are independent of self-reported family history of CHD. METH...

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Autores principales: Tada, Hayato, Melander, Olle, Louie, Judy Z., Catanese, Joseph J., Rowland, Charles M., Devlin, James J., Kathiresan, Sekar, Shiffman, Dov
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744619/
https://www.ncbi.nlm.nih.gov/pubmed/26392438
http://dx.doi.org/10.1093/eurheartj/ehv462
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author Tada, Hayato
Melander, Olle
Louie, Judy Z.
Catanese, Joseph J.
Rowland, Charles M.
Devlin, James J.
Kathiresan, Sekar
Shiffman, Dov
author_facet Tada, Hayato
Melander, Olle
Louie, Judy Z.
Catanese, Joseph J.
Rowland, Charles M.
Devlin, James J.
Kathiresan, Sekar
Shiffman, Dov
author_sort Tada, Hayato
collection PubMed
description AIMS: Genetic risk scores (GRSs) have been associated with coronary heart disease (CHD) in large studies. We asked whether expanding an established 27-variant GRS (GRS27) to a 50-variant GRS (GRS50) improved CHD prediction and whether GRSs are independent of self-reported family history of CHD. METHODS AND RESULTS: The association between GRSs and incident CHD was assessed in Cox models adjusting for established risk factors in 23 595 participants of the Malmö Diet and Cancer study—a prospective, population-based study. During a median follow-up of 14.4 years, 2213 participants experienced a first CHD event. After adjustment for established risk factors, both GRS27 and GRS50 were associated with incident CHD [hazard ratio (HR) = 1.70 for high (top quintile) vs. low (bottom quintile) of GRS27; 95% confidence interval (CI): 1.48–1.94; P(trend) = 1.6 × 10(−15) and HR = 1.92 for GRS50; 95% CI: 1.67–2.20; P(trend) = 6.2 × 10(−22)]. Adding 23 single nucleotide polymorphisms (SNPs) to GRS27 improved risk prediction (P = 3 × 10(−6)). Further adjustment for self-reported family history did not appreciably change the risk estimates of either GRS27 (HR = 1.65; 95% CI: 1.45–1.89) or GRS50 (HR = 1.87; 95% CI: 1.63–2.14). The addition of GRS50 to established risk factors, including self-reported family history, improved discrimination (P < 0.0001) and reclassification (continuous net reclassification improvement index = 0.17, P < 0.0001). In young participants (below median age), those with high GRS50 had 2.4-fold greater risk (95% CI: 1.85–3.12) than those with low GRS50. CONCLUSION: The addition of 23 SNPs to an existing GRS27 improved CHD risk prediction and was independent of self-reported family history. Coronary heart disease risk assessment by GRS could be particularly useful in young individuals.
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spelling pubmed-47446192016-02-08 Risk prediction by genetic risk scores for coronary heart disease is independent of self-reported family history Tada, Hayato Melander, Olle Louie, Judy Z. Catanese, Joseph J. Rowland, Charles M. Devlin, James J. Kathiresan, Sekar Shiffman, Dov Eur Heart J Clinical Research AIMS: Genetic risk scores (GRSs) have been associated with coronary heart disease (CHD) in large studies. We asked whether expanding an established 27-variant GRS (GRS27) to a 50-variant GRS (GRS50) improved CHD prediction and whether GRSs are independent of self-reported family history of CHD. METHODS AND RESULTS: The association between GRSs and incident CHD was assessed in Cox models adjusting for established risk factors in 23 595 participants of the Malmö Diet and Cancer study—a prospective, population-based study. During a median follow-up of 14.4 years, 2213 participants experienced a first CHD event. After adjustment for established risk factors, both GRS27 and GRS50 were associated with incident CHD [hazard ratio (HR) = 1.70 for high (top quintile) vs. low (bottom quintile) of GRS27; 95% confidence interval (CI): 1.48–1.94; P(trend) = 1.6 × 10(−15) and HR = 1.92 for GRS50; 95% CI: 1.67–2.20; P(trend) = 6.2 × 10(−22)]. Adding 23 single nucleotide polymorphisms (SNPs) to GRS27 improved risk prediction (P = 3 × 10(−6)). Further adjustment for self-reported family history did not appreciably change the risk estimates of either GRS27 (HR = 1.65; 95% CI: 1.45–1.89) or GRS50 (HR = 1.87; 95% CI: 1.63–2.14). The addition of GRS50 to established risk factors, including self-reported family history, improved discrimination (P < 0.0001) and reclassification (continuous net reclassification improvement index = 0.17, P < 0.0001). In young participants (below median age), those with high GRS50 had 2.4-fold greater risk (95% CI: 1.85–3.12) than those with low GRS50. CONCLUSION: The addition of 23 SNPs to an existing GRS27 improved CHD risk prediction and was independent of self-reported family history. Coronary heart disease risk assessment by GRS could be particularly useful in young individuals. Oxford University Press 2016-02-07 2015-09-20 /pmc/articles/PMC4744619/ /pubmed/26392438 http://dx.doi.org/10.1093/eurheartj/ehv462 Text en © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Clinical Research
Tada, Hayato
Melander, Olle
Louie, Judy Z.
Catanese, Joseph J.
Rowland, Charles M.
Devlin, James J.
Kathiresan, Sekar
Shiffman, Dov
Risk prediction by genetic risk scores for coronary heart disease is independent of self-reported family history
title Risk prediction by genetic risk scores for coronary heart disease is independent of self-reported family history
title_full Risk prediction by genetic risk scores for coronary heart disease is independent of self-reported family history
title_fullStr Risk prediction by genetic risk scores for coronary heart disease is independent of self-reported family history
title_full_unstemmed Risk prediction by genetic risk scores for coronary heart disease is independent of self-reported family history
title_short Risk prediction by genetic risk scores for coronary heart disease is independent of self-reported family history
title_sort risk prediction by genetic risk scores for coronary heart disease is independent of self-reported family history
topic Clinical Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744619/
https://www.ncbi.nlm.nih.gov/pubmed/26392438
http://dx.doi.org/10.1093/eurheartj/ehv462
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