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Proteomics Profiling and Risk of New-Onset Atrial Fibrillation: Framingham Heart Study

dc.contributor.authorKo, Darae
dc.contributor.authorBenson, Mark D.
dc.contributor.authorNgo, Debby
dc.contributor.authorYang, Qiong
dc.contributor.authorLarson, Martin G.
dc.contributor.authorWang, Thomas J.
dc.contributor.authorTrinquart, Ludovic
dc.contributor.authorMcManus, David D.
dc.contributor.authorLubitz, Steven A.
dc.contributor.authorEllinor, Patrick T.
dc.contributor.authorVasan, Ramachandran S.
dc.contributor.authorGerszten, Robert E.
dc.contributor.authorBenjamin, Emelia J.
dc.contributor.authorLin, Honghuang
dc.identifier.citationKo, D., Benson, M. D., Ngo, D., Yang, Q., Larson, M. G., Wang, T. J., Trinquart, L., McManus, D. D., Lubitz, S. A., Ellinor, P. T., Vasan, R. S., Gerszten, R. E., Benjamin, E. J., & Lin, H. (2019). Proteomics Profiling and Risk of New-Onset Atrial Fibrillation: Framingham Heart Study. Journal of the American Heart Association, 8(6), e010976.
dc.description.abstractBackground-Prior studies relating proteomics markers to incident AF screened for limited numbers of proteins. Methods and Results-We performed proteomics assays among participants from the Framingham Heart Study Offspring attending their fifth examination. Plasma protein levels (n=1373) were measured by the SOMAscan proteomic profiling platform. We used robust inference for the Cox proportional hazards model to relate each protein level with incident AF. In addition, we examined the association between AF-related genetic loci and levels of proteins associated with AF. Our study included 1885 participants (mean age 55 +/- 10 years, 54% women) who had proteomic profiles measured. A total of 349 participants developed AF during follow-up (mean follow-up 18.3 years). We observed that 8 proteins were significantly associated with incident AF after adjusting for age, sex, technical covariates, and correction for multiple testing (P<0.05/1373=3.6 x 10(-5)). After additional adjustments for clinical factors associated with AF, ADAMTS13 and N-terminal pro-B-type natriuretic peptide remained significantly associated with the risk of incident AF (hazard ratio, 0.78; 95% CI, 0.70-0.88; and 1.44; 95% CI, 1.22-1.70, respectively; P<3.6 x 10(-5) for both). None of the 8 proteins were encoded by genes at AF-related genetic loci previously identified by genome-wide association studies. Conclusions-We identified 8 proteins associated with risk of incident AF after adjustment for age and sex; 2 proteins were associated with AF after adjustment for AF risk factors. Future studies are needed to replicate our findings, identify whether the markers are mechanistically related to AF development, and whether they are clinically useful for identification of future AF risk.en_US
dc.description.sponsorshipThe study was supported by NIH contracts HHSN268201500001I and N01-HC 25195 to the Framingham Heart Study. Dr Benson is supported by the John S LaDue Memorial Fellowship at Harvard Medical School. Drs Trinquart and Lubitz are supported by American Heart Association 18SFRN34250007. Dr Lubitz is also supported by NIH grant 1R01HL139731 and a Doris Duke Charitable Foundation Clinical Scientist Development Award 2014105. Dr McManus is supported by NIH grants 5R01HL126911, 1R01HL137734, 1R01HL137794, 5R01HL135219-02, and 5UH3TR000921-04, as well as NSF grant NSF-12-512. Dr. Lin is supported in part by the Boston University Digital Health Initiative, Boston University Alzheimer's Disease Center Pilot Grant, and the National Center for Advancing Translational Sciences, National Institutes of Health, through BU-CTSI Grant Number 1UL1TR001430. Dr Vasan is supported in part by the Evans Medical Foundation and Jay and Louis Coffman Endowment, Boston University School of Medicine. Drs Wang and Gerszten are supported by NIH grants 5R01DK081572-10, 5R01HL132320-03, and 5R01DK108159-04. Drs Benjamin and Ellinor are supported by NIH grants 1R01HL128914; 2R01 HL092577; and American Heart Association 18SFRN341100825.en_US
dc.publisherJournal of the American Heart Associationen_US
dc.rightsCopyright © 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
dc.subjectatrial fibrillationen_US
dc.titleProteomics Profiling and Risk of New-Onset Atrial Fibrillation: Framingham Heart Studyen_US

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