TY - JOUR
T1 - Proteomic signatures of lifestyle risk factors for cardiovascular disease
T2 - A cross-sectional analysis of the plasma proteome in the framingham heart study
AU - Corlin, Laura
AU - Lin, Honghuang
AU - Leone, Dominick
AU - Yang, Qiong
AU - Ngo, Debby
AU - Levy, Daniel
AU - Adrienne Cupples, L.
AU - Gerszten, Robert E.
AU - Larson, Martin G.
AU - Vasan, Ramachandran S.
N1 - Publisher Copyright:
© 2020 The Authors.
PY - 2021
Y1 - 2021
N2 - BACKGROUND: Proteomic biomarkers related to cardiovascular disease risk factors may offer insights into the pathogenesis of cardiovascular disease. We investigated whether modifiable lifestyle risk factors for cardiovascular disease are associated with distinctive proteomic signatures. METHODS AND RESULTS: We analyzed 1305 circulating plasma proteomic biomarkers (assayed using the SomaLogic platform) in 897 FHS (Framingham Heart Study) Generation 3 participants (mean age 46±8 years; 56% women; discovery sample) and 1121 FOS (Framingham Offspring Study) participants (mean age 52 years; 54% women; validation sample). Participants were free of hypertension, diabetes mellitus, and clinical cardiovascular disease. We used linear mixed effects models (adjusting for age, sex, body mass index, and family structure) to relate levels of each inverse-log transformed protein to 3 lifestyle factors (ie, smoking, alcohol consumption, and physical activity). A Bonferroni-adjusted P value indicated statistical significance (based on number of proteins and traits tested, P<4.2×10-6 in the discovery sample P<6.85×10-4 in the validation sample). We observed statistically significant associations of 60 proteins with smoking (37/40 top proteins validated in FOS), 30 proteins with alcohol consumption (23/30 proteins validated), and 5 proteins with physical activity (2/3 proteins associated with the physical activity index validated). We assessed the associations of protein concentrations with previously identified genetic variants (protein quantitative trait loci) linked to lifestyle-related disease traits in the genome-wide-association study catalogue. The protein quantitative trait loci were associated with coronary artery disease, inflammation, and age-related mortality. CONCLUSIONS: Our cross-sectional study from a community-based sample elucidated distinctive sets of proteins associated with 3 key lifestyle factors.
AB - BACKGROUND: Proteomic biomarkers related to cardiovascular disease risk factors may offer insights into the pathogenesis of cardiovascular disease. We investigated whether modifiable lifestyle risk factors for cardiovascular disease are associated with distinctive proteomic signatures. METHODS AND RESULTS: We analyzed 1305 circulating plasma proteomic biomarkers (assayed using the SomaLogic platform) in 897 FHS (Framingham Heart Study) Generation 3 participants (mean age 46±8 years; 56% women; discovery sample) and 1121 FOS (Framingham Offspring Study) participants (mean age 52 years; 54% women; validation sample). Participants were free of hypertension, diabetes mellitus, and clinical cardiovascular disease. We used linear mixed effects models (adjusting for age, sex, body mass index, and family structure) to relate levels of each inverse-log transformed protein to 3 lifestyle factors (ie, smoking, alcohol consumption, and physical activity). A Bonferroni-adjusted P value indicated statistical significance (based on number of proteins and traits tested, P<4.2×10-6 in the discovery sample P<6.85×10-4 in the validation sample). We observed statistically significant associations of 60 proteins with smoking (37/40 top proteins validated in FOS), 30 proteins with alcohol consumption (23/30 proteins validated), and 5 proteins with physical activity (2/3 proteins associated with the physical activity index validated). We assessed the associations of protein concentrations with previously identified genetic variants (protein quantitative trait loci) linked to lifestyle-related disease traits in the genome-wide-association study catalogue. The protein quantitative trait loci were associated with coronary artery disease, inflammation, and age-related mortality. CONCLUSIONS: Our cross-sectional study from a community-based sample elucidated distinctive sets of proteins associated with 3 key lifestyle factors.
KW - Alcohol consumption
KW - Lifestyle
KW - Physical activity
KW - Proteomics
KW - Smoking
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U2 - 10.1161/JAHA.120.018020
DO - 10.1161/JAHA.120.018020
M3 - Article
C2 - 33372532
AN - SCOPUS:85099428287
SN - 2047-9980
VL - 10
SP - 1
EP - 16
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 1
M1 - e018020
ER -