rs11783655 (PLEC): Lipids, Height, and Tissue Expression

Key takeaways

• rs11783655 sits near the PLEC gene and has been identified in large genetic studies of serum lipid levels and adult height.
• The ALT allele of this variant is linked to reduced PLEC expression across seven distinct tissue types, most notably spleen and cultured fibroblasts.
• A second gene at the same locus, ENSG00000301024, shows reduced expression in testis tissue associated with this variant.
• Evidence comes from a lipid study of 94,674 multi-ethnic participants and a height meta-analysis of 253,288 European-ancestry individuals.
• No confirmed drug-response or lifestyle interactions have been reported for this specific variant.

What the research says A GWAS (genome-wide association study, a large scan of genetic variants across many people) of serum lipid levels using longitudinal electronic health record measurements from 94,674 multi-ethnic participants identified novel lipid-associated loci, with the PLEC region among those implicated. A separate GWAS meta-analysis of adult height in 253,288 European-ancestry individuals from 79 studies identified 697 height-associated variants that together explain approximately one-fifth of height heritability. GTEx v11 eQTL data (eQTL: a DNA variant linked to changes in gene expression levels) from 953 donors independently confirm that the ALT allele at rs11783655 is associated with reduced PLEC expression across seven tissues at highly significant p-values GTEx Portal.

Reported associations

• Serum lipid levels: This variant was identified in a multi-ethnic GWAS of 94,674 participants that measured HDL (high-density lipoprotein, sometimes called good cholesterol), LDL (low-density lipoprotein), triglycerides (blood fats), and total cholesterol using longitudinal untreated measurements from electronic health records, and that found 46 novel lipid-associated loci.
• Adult height: The locus was captured in a meta-analysis of 253,288 European-ancestry individuals that identified 697 genome-wide significant height variants together explaining roughly one-fifth of phenotypic height variance.
• PLEC tissue expression: The ALT allele is associated with reduced PLEC expression in spleen, cultured fibroblasts, pituitary, thyroid, lung, tibial nerve, and whole blood GTEx Portal.
• ENSG00000301024 testis expression: The ALT allele is also associated with reduced expression of this nearby gene specifically in testis (p=1.7e-42) GTEx Portal.

Evidence quality The lipid GWAS enrolled 94,674 GERA cohort participants with an average of 5.0 untreated lipid measurements per person, boosting statistical power through repeated measurements. Of 46 novel loci discovered in that study, 17 Bonferroni-replicated (passed a strict statistical correction for multiple testing) in 94,595 European-ancestry Global Lipids Genetics Consortium individuals, and 14 more reached nominal significance in 460,088 UK Biobank participants; the specific replication status of this locus is not detailed in the available excerpts. The height meta-analysis spanned 79 studies of 253,288 European-ancestry individuals, with directional consistency exceeding 99% in a Metabochip replication set of 80,067 individuals. Effect sizes specific to rs11783655 for lipid or height associations are not reported in the provided study excerpts, so individual variant strength cannot be precisely assessed from the data reviewed here. The eQTL evidence is highly robust: p-values reach 4.8e-125 in cultured fibroblasts and 2.6e-77 in whole blood, reflecting reproducible gene-regulation signals; these eQTL associations reflect tissue-level expression mechanisms and do not directly imply disease outcomes GTEx Portal. No conflicting findings between the two GWAS studies are apparent from the information available.

Tissue-specific expression effects

• PLEC: The ALT allele (the non-reference genetic variant) is associated with reduced expression across seven tissues: spleen (p=2.9e-36), cultured fibroblasts (p=4.8e-125), pituitary (p=1.5e-46), thyroid (p=3.7e-88), lung (p=7.5e-48), tibial nerve (p=5.2e-52), and whole blood (p=2.6e-77) GTEx Portal.
• ENSG00000301024: The ALT allele is associated with reduced expression of this nearby gene in testis (p=1.7e-42) GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.