Expressive

rs11136341 (PLEC): Blood Lipids and Tissue Expression

Key takeaways

  • rs11136341 sits near the PLEC gene and has been studied in large genome-wide analyses of blood lipid levels involving up to 188,000 participants
  • The alternative allele reduces PLEC expression in six tissues: spleen, cultured fibroblasts, pituitary gland, thyroid, testis, and whole blood
  • A second nearby gene (ENSG00000301024) also shows reduced expression in testis and whole blood with this allele
  • The supporting lipid GWAS studies covered multiple ancestries including European, East Asian, South Asian, and African American populations
  • GTEx eQTL associations for PLEC reach p-values as low as 8.6e-72 in cultured fibroblasts across 953 donors

Key takeaways

  • rs11136341 sits near the PLEC gene and has been studied in large genome-wide analyses of blood lipid levels involving up to 188,000 participants
  • The alternative allele reduces PLEC expression across six body tissues: spleen, cultured fibroblasts, pituitary gland, thyroid, testis, and whole blood
  • A second nearby gene (ENSG00000301024) also shows reduced expression in testis and whole blood with this allele
  • The supporting GWAS studies spanned multiple ancestries, including European, East Asian, South Asian, and African American populations
  • GTEx eQTL associations for PLEC reach p-values as low as 8.6e-72 in cultured fibroblasts across 953 donors

What the research says Three large genome-wide association studies (GWAS) of serum lipids collectively involved more than 188,000 individuals of European ancestry plus non-European cohorts, and a separate multi-ethnic electronic health record cohort of 94,674 individuals used 478,866 repeated lipid measurements to identify genome-wide significant loci (P < 5e-8) for LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglycerides (TG), and total cholesterol (TC). A UK Biobank factor analysis distilling hundreds of phenotypic variables into 35 latent constructs provided additional context for the broader genetic architecture. GTEx expression-quantitative trait locus (eQTL) data from 953 donors show that rs11136341 is associated with reduced PLEC expression in six tissues and reduced expression of a second nearby gene, ENSG00000301024, in two tissues GTEx Portal.

Reported associations

  • LDL cholesterol: Genome-wide significant associations (P < 5e-8) were identified at loci in this region in large multi-cohort GWAS; newly identified loci in one 2014 study explained approximately 2.4% of LDL-C variance in the Framingham offspring cohort
  • HDL cholesterol: HDL-C associations at genome-wide significance were found across European, East Asian, South Asian, and African American populations; newly identified loci in one study explained approximately 1.6% of HDL-C variance in the Framingham offspring
  • Triglycerides: Genome-wide significant TG associations were identified in this region; newly identified loci explained approximately 2.1% of TG variance in the Framingham offspring
  • Total cholesterol: TC associations were identified at genome-wide significance in multi-cohort meta-analyses; newly identified loci explained approximately 2.6% of TC variance

Evidence quality Three lipid GWAS studies underlie this locus: a 2010 meta-analysis of more than 100,000 European-ancestry individuals (validated in East Asian, South Asian, and African American cohorts) reporting that the full set of identified loci explained 9.6% (TG) to 12.4% (TC) of trait variance, corresponding to roughly 25-30% of estimated genetic variance; a 2014 study of 188,578 European-ancestry individuals identifying 62 additional novel loci; and a 2019 EHR-based multi-ethnic cohort of 94,674 individuals using 478,866 repeated measurements that increased variance explained by 33-42% compared to a single measurement. A UK Biobank factor analysis distilling hundreds of variables into 35 latent constructs provides supplementary phenome-wide context. The provided study excerpts do not report a variant-specific p-value, effect size, or odds ratio for rs11136341 individually, which limits assessment of its independent contribution to lipid traits. The GTEx eQTL evidence for this gene is statistically robust, with p-values spanning 1.2e-26 (spleen) to 8.6e-72 (cultured fibroblasts) across six tissues in 953 donors; ENSG00000301024 associations in testis (p = 2.8e-51) and whole blood (p = 1.6e-36) are similarly well-powered. All eQTL effects are in the same direction (reduced expression), with no conflicting signals in the provided data.

Tissue-specific expression effects

  • PLEC: Reduced expression in spleen, cultured fibroblasts, pituitary gland, thyroid, testis, and whole blood GTEx Portal
  • ENSG00000301024: Reduced expression in testis and 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.

Bloodwork

  • LDL cholesterol screening Moderate

    Genetic variant associated with elevated LDL cholesterol levels in large population cohorts.

Diet

  • Dietary LDL cholesterol reduction Moderate

    Carriers of the risk allele have genetically elevated LDL; diet can help mitigate this effect.

    Increase fiber, reduce saturated fat, add plant sterols; consider DASH or Mediterranean diet pattern.

Discuss with your doctor

  • Genetic predisposition to elevated LDL cholesterol Moderate

    This genetic variant is strongly associated with higher LDL cholesterol, informing cardiovascular risk assessment.

Frequently asked questions

What is rs11136341?

rs11136341 is a single-nucleotide polymorphism (a one-letter change in DNA) near the PLEC gene. It has been studied in large genome-wide analyses of blood lipid levels and is associated with reduced PLEC gene activity across six body tissues.

Is rs11136341 linked to cholesterol or triglycerides?

This variant falls in a region studied in large GWAS of LDL cholesterol, HDL cholesterol, triglycerides, and total cholesterol involving 94,000 to 188,000 participants. Those studies identified genome-wide significant associations at loci in this region, though the specific effect size for rs11136341 alone is not reported in the available study excerpts.

Which tissues does rs11136341 affect?

GTEx data from 953 donors show that the alternative allele is associated with reduced PLEC expression in six tissues: spleen, cultured fibroblasts, pituitary gland, thyroid, testis, and whole blood. A second nearby gene, ENSG00000301024, also shows reduced expression in testis and whole blood.

How strong is the evidence for rs11136341?

The supporting lipid GWAS studies enrolled up to 188,000 participants from multiple ancestries and applied strict genome-wide significance thresholds. The GTEx eQTL evidence is based on 953 donors and reaches p-values as low as 8.6e-72, indicating highly consistent associations.

Does rs11136341 affect more than one gene?

Yes. GTEx data show rs11136341 is associated with reduced expression of PLEC in six tissues and with reduced expression of a second nearby gene, ENSG00000301024, in testis and whole blood.