Association Between Genetically Determined Serum Corin and the Risk of Stroke in Chinese Adults: A Mendelian
Yang Liu1, Linan Chen2,3, Guozhe Sun4
1Department of Cardiology The First Affiliated Hospital of Soochow University Suzhou China.
Insights
Genetically determined higher serum corin levels are linked to an increased risk of stroke in Chinese adults. This Mendelian randomization study suggests elevated corin may causally contribute to stroke incidence.
Area of Science:
- Cardiovascular research
- Genetic epidemiology
- Biomarker discovery
Background:
- Observational studies suggest a link between serum corin and stroke.
- Causality between corin levels and stroke risk remains uncertain.
Purpose of the Study:
- To investigate the causal association between serum corin and stroke risk.
- Utilize Mendelian randomization to assess causality.
Main Methods:
- Mendelian randomization study design.
- Genotyping of single-nucleotide polymorphisms (SNPs) in the CORIN gene.
- Assay of serum corin and prospective follow-up for stroke incidents in 2310 Chinese adults.
Main Results:
- One SNP (rs2271037) in CORIN significantly associated with serum corin and stroke risk.
- Genetic risk score derived from SNP-corin associations showed a significant link to stroke.
- Mendelian randomization analyses consistently indicated a causal effect of higher serum corin on stroke risk.
Conclusions:
- Genetically determined variations in serum corin concentration are significantly associated with stroke risk.
- Elevated serum corin is identified as a potential causal risk factor for stroke in Chinese adults.
Background:
Serum corin has been associated with stroke in observational studies, but the underlying causality is uncertain. This study examined the causal association between corin and stroke through Mendelian randomization study.
Methods And Results:
In the Gusu cohort, serum corin was assayed at baseline, and stroke incidents were prospectively obtained during 10 years of follow-up. Single-nucleotide polymorphisms (SNPs) in CORIN were genotyped by MassArray for 2310 participants (mean age, 53 years; 39% men). Seventeen SNPs passed the Hardy-Weinberg test and were considered the potential instruments. Only 1 SNP (rs2271037) determined variability of serum corin was significantly associated with stroke even after adjusting for conventional risk factors (hazard ratio [HR], 1.36 [95% CI, 1.00-1.85]). The weighted genetic risk score generated from the SNP-corin associations was significantly associated with stroke (HR, 2.01 [95% CI, 1.15-3.51]). Using this genetic risk score as the instrument, 1-sample Mendelian randomization analysis found a significant HR of stroke per-SD higher log2-transformed corin (HR, 1.37 [95% CI, 1.07-1.76]). The inverse variance-weighted analysis based on the SNP-corin and SNP-stroke associations found that the HR of stroke pre-SD higher log2-transformed corin was 5.92 (95% CI, 2.23-15.72). The effect estimates stayed consistent regardless of an individual SNP being removed from the instruments. An almost identical effect estimate was also confirmed by multiple other 2-sample Mendelian randomization methods.
Conclusions:
Genetically determined variations of serum corin concentration were significantly associated with the risk of stroke in Chinese adults. Elevated serum corin may be a risk factor for stroke.
