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Feitosa MF, Kuipers AL, Wojczynski MK, et al. Heterogeneity of the Predictive Polygenic Risk Scores for Coronary Heart Disease Age-at-Onset in Three Different Coronary Heart Disease Family-Based Ascertainments. Circ Genom Precis Med. 2021;14(3):e003201doi: 10.1161/CIRCGEN.120.003201.
Feitosa, M. F., Kuipers, A. L., Wojczynski, M. K., Wang, L., Barinas-Mitchell, E., Kulminski, A. M., Thyagarajan, B., Lee, J. H., Perls, T., Christensen, K., Newman, A. B., Zmuda, J. M., & Province, M. A. (2021). Heterogeneity of the Predictive Polygenic Risk Scores for Coronary Heart Disease Age-at-Onset in Three Different Coronary Heart Disease Family-Based Ascertainments. Circulation. Genomic and precision medicine, 14(3), e003201. https://doi.org/10.1161/CIRCGEN.120.003201
Feitosa, Mary F, et al. "Heterogeneity of the Predictive Polygenic Risk Scores for Coronary Heart Disease Age-at-Onset in Three Different Coronary Heart Disease Family-Based Ascertainments." Circulation. Genomic and precision medicine vol. 14,3 (2021): e003201. doi: https://doi.org/10.1161/CIRCGEN.120.003201
Feitosa MF, Kuipers AL, Wojczynski MK, Wang L, Barinas-Mitchell E, Kulminski AM, Thyagarajan B, Lee JH, Perls T, Christensen K, Newman AB, Zmuda JM, Province MA. Heterogeneity of the Predictive Polygenic Risk Scores for Coronary Heart Disease Age-at-Onset in Three Different Coronary Heart Disease Family-Based Ascertainments. Circ Genom Precis Med. 2021 Jun;14(3):e003201. doi: 10.1161/CIRCGEN.120.003201. Epub 2021 Apr 12. PMID: 33844929; PMCID: PMC8214825.
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Circ Genom Precis Med. 2021 Jun;14(3):e003201. doi: 10.1161/CIRCGEN.120.003201. Epub 2021 Apr 12.

Heterogeneity of the Predictive Polygenic Risk Scores for Coronary Heart Disease Age-at-Onset in Three Different Coronary Heart Disease Family-Based Ascertainments.

Circulation. Genomic and precision medicine

Mary F Feitosa, Allison L Kuipers, Mary K Wojczynski, Lihua Wang, Emma Barinas-Mitchell, Alexander M Kulminski, Bharat Thyagarajan, Joseph H Lee, Thomas Perls, Kaare Christensen, Anne B Newman, Joseph M Zmuda, Michael A Province

Affiliations

  1. Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO (M.F.F., M.K.W., L.W., M.A.P.).
  2. Department of Epidemiology (A.L.K., E.B.-M., A.B.N., J.M.Z.), University of Pittsburgh, PA.
  3. Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, NC (A.M.K.).
  4. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (B.T.).
  5. Sergievsky Center, Taub Institute, Department of Epidemiology and Department of Neurology, Columbia University, NY (J.H.L.).
  6. Department of Medicine, Boston University School of Medicine, MA (T.P.).
  7. Danish Aging Research Center, University of Southern Denmark, Odense C (K.C.).
  8. Department of Human Genetics (J.M.Z.), University of Pittsburgh, PA.

PMID: 33844929 PMCID: PMC8214825 DOI: 10.1161/CIRCGEN.120.003201

Abstract

BACKGROUND: Polygenic risk scores (PRS) for coronary heart disease (CHD) may contribute to assess the overall risk of CHD. We evaluated how PRS may influence CHD risk when the distribution of age-at-onset, sex, and family health history differ significantly.

METHODS: Our study included 3 family-based ascertainments: LLFS (Long Life Family Study, N

RESULTS: Healthy-aging LLFS presented ≈17 years delayed for CHD age-at-onset compared with FamHS-high risk (

CONCLUSIONS: Differences in CHD family-based ascertainments show evidence of PRS interacting with sex to predict CHD risk. In women, CHD age-at-onset was associated with PRS, CHD family history, and interactions of PRS with family history. In men, PRS and CHD family history were the major effects on the CHD age-at-onset. Understanding the heterogeneity of risks associated with CHD end points at both the personal and familial levels may shed light on the underlying genetic effects influencing CHD and lead to more personalized risk prediction.

Keywords: aging; cardiovascular diseases; coronary artery disease; risk factors

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