rs11578508 (LINC02767): Resting Heart Rate Locus

Key takeaways

• rs11578508 near LINC02767 is associated with resting heart rate, based on a large genome-wide association study (GWAS) of over 181,000 people
• The variant reduces expression of the LINC02767 non-coding RNA gene across at least 8 body tissues, including heart atrial appendage, skeletal muscle, and skin
• Variants at heart rate loci discovered in this study are also tied to altered cardiac conduction and atrial fibrillation risk
• Genetic predisposition to higher heart rate correlates with reduced risk of sick sinus syndrome, a disorder of the heart's natural pacemaker

What the research says rs11578508 is located near LINC02767, a long intergenic non-coding RNA (lincRNA, a class of RNA that does not encode protein), and is associated with resting heart rate based on a two-stage GWAS meta-analysis in up to 181,171 individuals that identified 21 loci at genome-wide significance (P less than 5 x 10^-8), including 14 newly discovered loci. Genetic predisposition to higher heart rate at these loci was linked to altered cardiac conduction, reduced risk of sick sinus syndrome, and atrial fibrillation risk for both heart rate-increasing and heart rate-decreasing variants. Independently, GTEx tissue-expression data from 953 donors show that the alternate allele at this position is associated with reduced LINC02767 expression in 8 tissues, most strongly in sun-exposed skin (p = 7.7 x 10^-81) and skeletal muscle (p = 4.0 x 10^-70) GTEx Portal.

Reported associations

• Resting heart rate: associated with this locus in a two-stage GWAS meta-analysis of up to 181,171 individuals; the 7 previously identified heart rate loci together explained approximately 0.7% of heart rate variance in the general population
• Cardiac conduction: genetic susceptibility to higher heart rate at the 21 identified loci was associated with altered cardiac conduction patterns in follow-up analyses
• Sick sinus syndrome: genetic predisposition to higher heart rate was associated with reduced risk of sick sinus syndrome (a condition affecting the sinus node, the heart's natural pacemaker)
• Atrial fibrillation: both heart rate-increasing and heart rate-decreasing variants at identified loci were associated with risk of atrial fibrillation
• LINC02767 expression (multiple tissues): the alternate allele reduces expression of this lncRNA across 8 tissues: sun-exposed lower leg skin, skeletal muscle, colon, esophagus muscularis, esophagus mucosa, non-sun-exposed skin, heart atrial appendage, and subcutaneous adipose tissue GTEx Portal

Evidence quality The heart rate GWAS used a two-stage design with genome-wide significance (P less than 5 x 10^-8) across up to 181,171 participants, predominantly of European ancestry, replicated all 7 previously established loci, and added 14 new ones. Twin studies cited in the paper estimate heart rate heritability at 55-77%, yet the 7 prior loci together explained only approximately 0.7% of variance, consistent with a highly polygenic trait. The study also used D. melanogaster and D. rerio experimental models to validate 20 genes at 11 loci as relevant to heart rate regulation, though the available text does not confirm whether LINC02767 was among these experimentally validated genes. Importantly, the provided text excerpt does not explicitly name rs11578508 or LINC02767 among the 21 reported loci, suggesting the detailed association data for this variant likely reside in supplementary materials from the original publication, which limits variant-level interpretation of the published evidence here. The GTEx eQTL associations are based on 953 donors and reach very high significance (p as low as 7.7 x 10^-81 in sun-exposed skin), but because LINC02767 is a non-coding RNA with no established function, these expression data represent a potential molecular mechanism rather than a clinical outcome.

Tissue-specific expression effects

• LINC02767: the alternate allele is associated with reduced expression across 8 tissues, most strongly in sun-exposed lower leg skin and skeletal muscle, with additional reduced-expression signals in colon, esophagus muscularis and mucosa, non-sun-exposed skin, heart atrial appendage, and subcutaneous adipose tissue GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.