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Abstract Background and Aims It is not clear how a polygenic risk score (PRS) can be best combined with guideline-recommended tools for cardiovascular disease (CVD) risk prediction, e.g. SCORE2.
Methods A PRS for coronary artery disease (CAD) was calculated in participants of UK Biobank (n = 432 981). Within each tenth of the PRS distribution, the odds ratios (ORs)—referred to as PRS-factor—for CVD (i.e. CAD or stroke) were compared between the entire population and subgroups representing the spectrum of clinical risk. Replication was performed in the combined Framingham/Atherosclerosis Risk in Communities (ARIC) populations (n = 10 757). The clinical suitability of a multiplicative model ‘SCORE2 × PRS-factor’ was tested by risk reclassification.
Results In subgroups with highly different clinical risks, CVD ORs were stable within each PRS tenth. SCORE2 and PRS showed no significant interactive effects on CVD risk, which qualified them as multiplicative factors: SCORE2 × PRS-factor = total risk. In UK Biobank, the multiplicative model moved 9.55% of the intermediate (n = 145 337) to high-risk group increasing the individuals in this category by 56.6%. Incident CVD occurred in 8.08% of individuals reclassified by the PRS-factor from intermediate to high risk, which was about two-fold of those remained at intermediate risk (4.08%). Likewise, the PRS-factor shifted 8.29% of individuals from moderate to high risk in Framingham/ARIC.
Conclusions This study demonstrates that absolute CVD risk, determined by a clinical risk score, and relative genetic risk, determined by a PRS, provide independent information. The two components may form a simple multiplicative model improving precision of guideline-recommended tools in predicting incident CVD.
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The cuttlebone, a chambered gas-filled structure found in cuttlefish, serves a crucial role in buoyancy control for the animal. This study investigates the motion of liquid-gas interfaces within cuttlebone-inspired artificial channels. The cuttlebone’s unique microstructure, characterized by chambers divided by vertical pillars, exhibits interesting fluid dynamics at small scales while pumping water in and out. Various channels were fabricated with distinct geometries, mimicking cuttlebone features, and subjected to different pressure drops. The behavior of the liquid-gas interface was explored, revealing that channels with pronounced waviness facilitated more non-uniform air-water interfaces. Here, Lyapunov exponents were employed to characterize interface separation, and they indicated more differential motions with increased pressure drops. Channels with greater waviness and amplitude exhibited higher Lyapunov exponents, while straighter channels exhibited slower separation. This is potentially aligned with cuttlefish’s natural adaptation to efficient water transport near the membrane, where more straight channels are observed in real cuttlebone.more » « lessFree, publicly-accessible full text available October 1, 2024
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