rs114655300 (LINC01365): Blood Pressure Variant

Key takeaways

• rs114655300, located near the long intergenic non-coding RNA genes LINC01365 and LINC02502, was identified as a novel blood pressure variant through a genome-wide pleiotropy analysis.
• The analysis drew on up to 757,601 individuals of European ancestry and 318,891 predominantly male multiethnic participants, providing a large discovery and replication base.
• This variant shows horizontal pleiotropy for blood pressure, meaning it appears to affect systolic and diastolic blood pressure through distinct biological pathways rather than one driving the other.
• Including horizontal pleiotropic variants like this one in a composite genetic risk score improved heritability capture for blood pressure traits by 1.11- to 3.26-fold and enhanced prediction of hypertension and cardiovascular disease.

What the research says rs114655300, near the LINC01365 and LINC02502 region (long intergenic non-coding RNA genes that produce RNA molecules but not proteins), was identified in a genome-wide horizontal pleiotropy analysis of systolic and diastolic blood pressure. The study used summary statistics from the UK Biobank combined with the International Consortium for Blood Pressure (up to 757,601 European-ancestry participants) as a discovery cohort, and the Million Veteran Program (318,891 predominantly male multiethnic participants) for replication or meta-analysis. In total, 118 novel pleiotropic blood pressure variants including 18 novel loci were replicated in the MVP cohort, while an additional 219 novel signals and 40 novel loci were identified through meta-analysis without further independent replication; the specific tier in which rs114655300 falls is not stated in the available study text.

Reported associations

• Systolic blood pressure: Identified as a novel horizontal pleiotropic variant in a blood pressure analysis spanning up to 757,601 European-ancestry participants with independent replication or meta-analysis in 318,891 multiethnic participants.
• Diastolic blood pressure: Identified in the same analysis as having horizontal pleiotropic effects on diastolic blood pressure, with pathways characterized as distinct from those affecting systolic blood pressure.
• Hypertension (genetic risk score): Composite genetic risk scores incorporating horizontal pleiotropic variants from this analysis improved Nagelkerke's R2 (a measure of explained variance in regression models) for hypertension by 1.09-fold over scores that excluded such variants.
• Cardiovascular disease (genetic risk score): The same composite scores improved Nagelkerke's R2 for cardiovascular disease by 2.01-fold, indicating that pleiotropic variants contribute meaningfully to genetic risk prediction beyond standard approaches.

Evidence quality The discovery phase used data from up to 757,601 European-ancestry participants in the UK Biobank and International Consortium for Blood Pressure; replication or meta-analysis involved 318,891 predominantly male multiethnic participants from the Million Veteran Program. A subset of 118 novel variants including 18 novel loci was replicated in the MVP cohort, while a further 219 novel signals and 40 novel loci from the combined meta-analysis lacked independent replication. Because the available study text does not name rs114655300 explicitly in the results section, it is unclear whether this variant falls in the replicated or non-replicated tier. No variant-specific effect size (such as an odds ratio or beta coefficient) for this locus is available in the provided text. The region contains non-coding RNA genes, and no functional mechanism linking it to blood pressure regulation is established by the available evidence.

Lifestyle considerations No lifestyle considerations on file for this variant.