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    题名: Genetic Risk Score Constructed from Common Genetic Variants is Associated with Cardiovascular Disease Risk in Type 2 Diabetes Mellitus
    作者: Cheng, Chi-Fung;Lin, Ying-Ju;Lin, Mei-Chen;Liang, Wen-Miin;Chen, Ching-Chu;Chen, ChienHsiun;Wu, Jer-Yuarn;Lin, Ting-Hsu;Liao, Chiu-Chu;Huang, Shao- Mei;Hsieh, Ai-Ru;Tsai, Fuu-Jen
    关键词: cardiovascular disease;cumulative effect;genetic risk score;genetic variant;type 2 diabetes mellitus
    日期: 2020-12-22
    上传时间: 2021-02-25 12:10:19 (UTC+8)
    摘要: Background
    Patients with type 2 diabetes mellitus (T2DM) experience a two‐fold increased risk of cardiovascular diseases. Genome‐wide association studies (GWAS) have identified T2DM susceptibility genetic variants. Interestingly, the genetic variants associated with cardiovascular disease risk in T2DM Han Chinese remain to be elucidated. The present study aimed to investigate the genetic variants associated with cardiovascular disease risk in T2DM.

    Methods
    We performed bootstrapping, GWAS and an investigation of genetic variants associated with cardiovascular disease risk in a discovery T2DM cohort and in a replication cohort. The discovery cohort included 326 cardiovascular disease patients and 1209 noncardiovascular disease patients. The replication cohort included 68 cardiovascular disease patients and 317 noncardiovascular disease patients. The main outcome measures were genetic variants for genetic risk score (GRS) in cardiovascular disease risk in T2DM.

    Results
    In total, 35 genetic variants were associated with cardiovascular disease risk. A GRS was generated by combining risk alleles from these variants weighted by their estimated effect sizes (log odds ratio [OR]). T2DM patients with weighted GRS ≥ 12.63 had an approximately 15‐fold increase in cardiovascular disease risk (odds ratio = 15.67, 95% confidence interval [CI] = 10.33–24.00) compared to patients with weighted GRS < 10.39. With the addition of weighted GRS, receiver‐operating characteristic curves showed that area under the curve with conventional risk factors was improved from 0.719 (95% CI = 0.689–0.750) to 0.888 (95% CI = 0.866–0.910).

    Conclusions
    These 35 genetic variants are associated with cardiovascular disease risk in T2DM, alone and cumulatively. T2DM patients with higher levels of weighted genetic risk score have higher cardiovascular disease risks.
    關聯: The Journal of Gene Medicine 23(2), e3305
    DOI: 10.1002/jgm.3305
    显示于类别:[統計學系暨研究所] 期刊論文

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