Expressive

rs11588151 (PCSK9): Multi-Tissue Expression Variant

Key takeaways

  • rs11588151 reduces PCSK9 gene expression across at least 7 tissues, including tibial nerve, brain, fat, lung, and blood
  • The same variant also reduces BSND expression in whole blood
  • The strongest documented effect is in tibial nerve tissue, with a log2 expression slope of −0.73
  • All current evidence comes from tissue gene-expression studies, not clinical disease outcomes
  • GTEx v11 analysis of 953 donors underpins all associations, with the tibial nerve effect reaching p = 4.1 × 10^-49

Key takeaways

  • rs11588151 reduces PCSK9 gene expression across at least 7 tissues, including tibial nerve, brain, fat, lung, and blood
  • The same variant also reduces BSND expression in whole blood
  • The strongest documented effect is in tibial nerve tissue, with a log2 expression slope of −0.73
  • All current evidence comes from tissue gene-expression studies, not clinical disease outcomes
  • GTEx v11 analysis of 953 donors underpins all associations, with the tibial nerve effect reaching p = 4.1 × 10^-49

What the research says GTEx v11 tissue expression analysis (953 donors, FDR < 0.05) identifies rs11588151 as an eQTL - a genetic variant that influences how much of a gene's RNA is produced in a cell - consistently linked to reduced PCSK9 expression across seven distinct tissues, with log2-normalized effect sizes (slopes) ranging from −0.13 in whole blood to −0.73 in tibial nerve GTEx Portal. The same variant is also associated with reduced BSND expression in whole blood (slope −0.39, p = 2.2 × 10^-²^7) GTEx Portal.

Reported associations

  • PCSK9 expression - tibial nerve: reduced expression (slope −0.73, p = 4.1 × 10^-49); the largest effect size recorded for this variant GTEx Portal
  • PCSK9 expression - visceral adipose (belly fat): reduced expression (slope −0.38, p = 1.4 × 10^-9) GTEx Portal
  • PCSK9 expression - brain cerebellum: reduced expression (slope −0.36, p = 2.2 × 10^-5) GTEx Portal
  • PCSK9 expression - lung: reduced expression (slope −0.28, p = 2.1 × 10^-¹^7) GTEx Portal
  • PCSK9 expression - cerebellar hemisphere: reduced expression (slope −0.27, p = 3.8 × 10^-5) GTEx Portal
  • PCSK9 expression - subcutaneous adipose (under-skin fat): reduced expression (slope −0.22, p = 1.6 × 10^-5) GTEx Portal
  • PCSK9 expression - whole blood: reduced expression (slope −0.13, p = 3.7 × 10^-6) GTEx Portal
  • BSND expression - whole blood: reduced expression (slope −0.39, p = 2.2 × 10^-²^7) GTEx Portal

Evidence quality All reported associations derive from GTEx v11 eQTL analysis (953 donors, FDR < 0.05, cis-window), a well-powered tissue gene-expression resource. Statistical significance is strong across all eight tissue-gene pairings, with p-values ranging from 3.8 × 10^-5 in cerebellar hemisphere to 4.1 × 10^-49 in tibial nerve; all eight effects point in the same direction (reduced expression for the alternate allele), with no conflicting findings within the provided evidence. These are gene-regulation observations, not clinical outcome data - no GWAS studies directly linking rs11588151 to a specific disease or trait are included in the provided evidence base. A gene-smoking interaction study of carotid intima-media thickness (cIMT - a measure of arterial wall thickness used as a proxy for atherosclerosis) in West African populations (AWI-Gen study, 1,776 men from Burkina Faso and Ghana) is provided as contextual background but does not report a direct phenotypic association for this variant.

Tissue-specific expression effects

  • PCSK9: reduced expression in seven tissues - tibial nerve (strongest effect), visceral adipose, brain cerebellum, lung, cerebellar hemisphere, subcutaneous adipose, and whole blood GTEx Portal
  • BSND: reduced expression in whole blood GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Lifestyle context

Concrete actions anchored to the cited research. We do not prescribe, we describe.

Lifestyle

  • smoking Moderate

    G allele carriers show accelerated subclinical atherosclerosis progression when exposed to smoking

    Quit if currently smoking; maintain avoidance if never smoked

Screening

  • carotid ultrasound screening Moderate

    This SNP modulates smoking-related atherosclerosis progression; periodic monitoring detects subclinical disease progression

    Discuss baseline assessment and monitoring schedule with clinician

Frequently asked questions

What does rs11588151 do?

rs11588151 is associated with reduced expression of PCSK9 across seven tissues - tibial nerve, visceral adipose, brain cerebellum, lung, cerebellar hemisphere, subcutaneous adipose, and whole blood - and reduced BSND expression in whole blood. These effects are measured in tissue samples from 953 donors in GTEx v11.

In which tissues does rs11588151 affect PCSK9 expression?

GTEx v11 eQTL data identifies seven affected tissues: tibial nerve (largest effect, slope −0.73), visceral adipose, brain cerebellum, lung, cerebellar hemisphere, subcutaneous adipose, and whole blood (smallest effect, slope −0.13).

What is an eQTL?

An eQTL, or expression quantitative trait locus, is a genetic variant statistically associated with differences in how much of a gene's RNA is produced in a given tissue. It describes gene regulation, not disease outcomes directly.

Is rs11588151 linked to any diseases?

The evidence provided for rs11588151 covers tissue gene-expression effects only. No GWAS studies directly linking this variant to clinical disease outcomes are included in the current evidence base.

How strong is the evidence for rs11588151's effects?

All associations come from GTEx v11 eQTL analysis of 953 tissue donors, with a false discovery rate below 0.05. All eight reported tissue effects consistently show reduced expression, with p-values ranging from 3.8 × 10^-5 to 4.1 × 10^-49, and no conflicting findings exist in the provided data.