Genetic risk score constructed from common genetic variants is associated with cardiovascular disease risk in type 2 diabetes mellitus

• Published in: The journal of gene medicine 2021-02, Vol.23 (2), p.e3305-n/a
• Main Authors: Cheng, Chi‐Fung, Lin, Ying‐Ju, Lin, Mei‐Chen, Liang, Wen‐Miin, Chen, Ching‐Chu, Chen, Chien‐Hsiun, Wu, Jer‐Yuarn, Lin, Ting‐Hsu, Liao, Chiu‐Chu, Huang, Shao‐Mei, Hsieh, Ai‐Ru, Tsai, Fuu‐Jen
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Aged; Alleles; Asians - genetics; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - genetics; Cohort Studies; Contactins - genetics; Cross-Sectional Studies; cumulative effect; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; DNA-Binding Proteins - genetics; Female; G-Protein-Coupled Receptor Kinase 4 - genetics; Gene therapy; Genetic diversity; Genetic Predisposition to Disease; genetic risk score; genetic variant; Genome-wide association studies; Genome-Wide Association Study; Genomes; Health risk assessment; Humans; Male; Middle Aged; Nerve Tissue Proteins - genetics; Odds Ratio; Polymorphism, Single Nucleotide; Replication; Risk Factors; ROC Curve; Transcription Factors - genetics; type 2 diabetes mellitus
• ISSN: 1099-498X; 1521-2254
• DOI: 10.1002/jgm.3305

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. Distribution of the cumulative weighted genetic risk score of 35 SNPs in T2DM patients (Cardiovascular patients: grey squares; Non‐cardiovascular: black squares).