rs11718848 (GOLGA4): Blood Pressure Association

Key takeaways

• Identified as a blood pressure-associated variant in a meta-analysis covering over 1.3 million participants across 92 studies.
• In this study, rare variants carried roughly 8 times the per-allele effect on blood pressure compared to common variants on average.
• GTEx data link the alternate allele to increased expression of GOLGA4 in esophagus mucosa, skeletal muscle, and skin.
• The same allele is linked to increased LRRFIP2 expression in thyroid and aortic tissues, and to reduced ITGA9 expression in whole blood.
• Blood pressure-associated variants in this study were enriched in fetal active chromatin regions, suggesting developmental pathways in blood pressure regulation.

What the research says A meta-analysis examining up to approximately 1.3 million participants across 92 studies identified 106 new blood pressure (BP)-associated genomic regions and 87 rare variant (minor allele frequency, or MAF, at or below 0.01) BP associations at genome-wide significance (P < 5 x 10-8). On average, rare variants in this study showed effects approximately 8 times larger than common variant effects on BP, and 44% of rare coding associations directly implicated candidate causal genes through amino acid changes. BP-associated variants were also enriched in active chromatin regions of fetal tissues, pointing to possible developmental origins of adult blood pressure differences.

Reported associations

• Blood pressure regulation: rs11718848 near the GOLGA4 locus was identified as a BP-associated variant in a meta-analysis of up to approximately 1.3 million participants; the specific BP trait (systolic, diastolic, pulse pressure, or hypertension) and per-allele effect size for this individual variant are not detailed in the provided study excerpt.

Evidence quality The BP association evidence comes from a single large meta-analysis of up to approximately 1.3 million participants across 92 studies, using the field-standard genome-wide significance threshold of P < 5 x 10-8, which is among the most statistically rigorous thresholds in human genetics. This is among the largest BP genetics analyses conducted to date, providing substantial statistical power for variant discovery. However, the specific p-value, effect size, and minor allele frequency for rs11718848 individually are not included in the provided study excerpt, so the relative strength of this particular association cannot be quantified here. The GTEx eQTL (expression quantitative trait locus - a genetic variant that influences how much a gene is expressed in a given tissue) data are derived independently from 953 donors at a false discovery rate below 5%, providing mechanistic evidence across multiple tissues. No replication data specific to this locus are described in the available study excerpt.

Tissue-specific expression effects

• LRRFIP2: the alternate allele is associated with increased expression across four tissues - most strongly in thyroid, followed by aorta, skeletal muscle, and esophagus muscularis GTEx Portal.
• GOLGA4: the alternate allele is associated with increased expression in esophagus mucosa, skeletal muscle, and sun-exposed lower leg skin GTEx Portal.
• ITGA9: the alternate allele is associated with reduced expression in whole blood GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.