rs117445861 (LINC02267): Metabolite QTL in CAD

Key takeaways

• rs117445861 is a novel metabolite quantitative trait locus (metaboQTL) near LINC02267 (a long intergenic non-coding RNA - a gene that produces RNA molecules but not proteins), meaning it associates with levels of circulating metabolites in the blood
• This finding comes from the first large-scale metabolomics genome-wide association study (GWAS) in a Han Chinese coronary artery disease (CAD) population, involving 1,551 patients across three clinical centers
• A metaboQTL links a genetic position to measurable metabolite levels; the specific metabolites tied to this variant are detailed in supplementary data from the source study
• Evidence is based on a single study with no independent replication reported in other populations, so this finding should be considered preliminary

What the research says A two-stage genome-wide association study of metabolites (metaboGWAS) in 1,551 Han Chinese patients with CAD tested 3,435,396 imputed (statistically inferred) single-nucleotide polymorphisms (SNPs - single-letter DNA changes) against 161 metabolites and 12,280 metabolite ratios. After applying Bonferroni-corrected thresholds (a stringent statistical cutoff accounting for testing many variants at once; p < 3.11 x 10^-10 for single metabolites; p < 3.88 x 10^-12 for ratios), 109 significant associations were confirmed across 14 SNPs, with rs117445861 among the novel metaboQTLs identified. The study used a discovery cohort (n=1,028) and a separate validation cohort (n=523) from three centers, adjusting for 10 principal components (statistical summaries of genetic ancestry used to control for population differences) and multiple clinical covariates including age, sex, hypertension, and kidney function.

Reported associations

• Plasma metabolite levels in CAD patients: rs117445861 was identified as a novel metaboQTL in Han Chinese patients with coronary artery disease, associating with one or more circulating plasma metabolites; it was reported for the first time in this study, with no prior documentation in the literature cited

Evidence quality The association was established in a two-stage design with a discovery cohort (n=1,028) and a validation cohort (n=523), both of Han Chinese patients with CAD from three clinical centers. The study applied strict Bonferroni-corrected significance thresholds and controlled for population stratification and multiple clinical confounders. Limitations include restriction to a single ethnic group and a population already diagnosed with CAD, meaning findings may not generalize to other populations or to disease-free individuals. No replication in non-Chinese cohorts is reported. The locus is described as a first-report novel finding with no prior established role in the cited literature. Specific effect sizes for this variant are in supplementary tables not reproduced in the available study text. Overall, this evidence is preliminary.

Lifestyle considerations No lifestyle considerations on file for this variant.