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        Development and External Validation of a Deep Learning Algorithm for Prognostication of Cardiovascular Outcomes

        In-Jeong Cho,Ji Min Sung,Hyeon Chang Kim,Sang Eun Lee,Myeong-Hun Chae,Maryam Kavousi,Oscar L. Rueda-Ochoa,M. Arfan Ikram,Oscar H. Franco,James K. Min,장혁재 대한심장학회 2020 Korean Circulation Journal Vol.50 No.1

        Background and Objectives: We aim to explore the additional discriminative accuracy of a deep learning (DL) algorithm using repeated-measures data for identifying people at high risk for cardiovascular disease (CVD), compared to Cox hazard regression. Methods: Two CVD prediction models were developed from National Health Insurance Service-Health Screening Cohort (NHIS-HEALS): a Cox regression model and a DL model. Performance of each model was assessed in the internal and 2 external validation cohorts in Koreans (National Health Insurance Service-National Sample Cohort; NHIS-NSC) and in Europeans (Rotterdam Study). A total of 412,030 adults in the NHIS-HEALS; 178,875 adults in the NHIS-NSC; and the 4,296 adults in Rotterdam Study were included. Results: Mean ages was 52 years (46% women) and there were 25,777 events (6.3%) in NHIS-HEALS during the follow-up. In internal validation, the DL approach demonstrated a C-statistic of 0.896 (95% confidence interval, 0.886–0.907) in men and 0.921 (0.908–0.934) in women and improved reclassification compared with Cox regression (net reclassification index [NRI], 24.8% in men, 29.0% in women). In external validation with NHIS-NSC, DL demonstrated a C-statistic of 0.868 (0.860–0.876) in men and 0.889 (0.876–0.898) in women, and improved reclassification compared with Cox regression (NRI, 24.9% in men, 26.2% in women). In external validation applied to the Rotterdam Study, DL demonstrated a C-statistic of 0.860 (0.824–0.897) in men and 0.867 (0.830–0.903) in women, and improved reclassification compared with Cox regression (NRI, 36.9% in men, 31.8% in women). Conclusions: A DL algorithm exhibited greater discriminative accuracy than Cox model approaches.

      • Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma

        Chambers, John C,Zhang, Weihua,Sehmi, Joban,Li, Xinzhong,Wass, Mark N,Van der Harst, Pim,Holm, Hilma,Sanna, Serena,Kavousi, Maryam,Baumeister, Sebastian E,Coin, Lachlan J,Deng, Guohong,Gieger, Christi Nature Publishing Group, a division of Macmillan P 2011 Nature genetics Vol.43 No.11

        Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10<SUP>??8</SUP> to P = 10<SUP>??190</SUP>). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function.

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