|標題：Genetic Risk Score Constructed from Common Genetic Variants is Associated with Cardiovascular Disease Risk in Type 2 Diabetes Mellitus|
|作品名稱||Genetic Risk Score Constructed from Common Genetic Variants is Associated with Cardiovascular Disease Risk in Type 2 Diabetes Mellitus|
|著者||Chi-Fung Cheng; Ying-Ju Lin; Mei-Chen Lin; Wen-Miin Liang; Ching-Chu Chen; ChienHsiun Chen; Jer-Yuarn Wu; Ting-Hsu Lin; Chiu-Chu Liao; Shao- Mei Huang; Ai-Ru Hsieh(謝璦如)*; Fuu-Jen Tsai*|
|著錄名稱、卷期、頁數||The Journal of Gene Medicine 23(2), e3305|
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.
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.
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).
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.
|關鍵字||cardiovascular disease;cumulative effect;genetic risk score;genetic variant;type 2 diabetes mellitus|