Expressive

rs11589568 (TRIM33): Height and Expression Variant

Key takeaways

  • rs11589568 was found to be significantly associated with adult height in a genome-wide study of more than 5.4 million people
  • The variant influences TRIM33 gene activity differently depending on the tissue type
  • In adrenal gland, fat tissue, breast tissue, and blood vessels, the variant is linked to higher TRIM33 expression
  • In testis and whole blood, the same variant is linked to lower TRIM33 expression
  • Height prediction accuracy from this and related common variants is strong in European-ancestry populations but lower in other ancestry groups

Key takeaways

  • rs11589568 was found to be significantly associated with adult height in a genome-wide study of more than 5.4 million people
  • The variant influences TRIM33 gene activity differently depending on the tissue type
  • In adrenal gland, fat tissue, breast tissue, and blood vessels, the variant is linked to higher TRIM33 expression
  • In testis and whole blood, the same variant is linked to lower TRIM33 expression
  • Height prediction accuracy from this and related common variants is strong in European-ancestry populations but lower in other ancestry groups

What the research says A genome-wide association study (GWAS - a method that scans the genome for positions where DNA differences correlate with a trait) of more than 5.4 million individuals across 281 studies identified rs11589568 as one of 12,111 independent SNPs significantly associated with adult height; together these SNPs explain approximately 40% of height variation in European-ancestry populations. GTEx v11 data (953 donors, FDR < 0.05) further show that rs11589568 is a cis-eQTL for TRIM33 (an expression quantitative trait locus - meaning this variant is statistically associated with differences in how much the TRIM33 gene is expressed in nearby cells), with the direction of that effect depending on the tissue examined GTEx Portal.

Reported associations

  • Adult height: One of 12,111 common SNPs achieving genome-wide significance in a meta-analysis of 5,380,080 individuals across 281 studies; the full set of 12,111 SNPs collectively explains approximately 40% of height variance (approximately 45% using all HapMap 3 panel SNPs) in European-ancestry samples
  • TRIM33 expression (increased in multiple tissues): The ALT allele is associated with increased TRIM33 expression in adrenal gland (slope +0.18, p=7.7e-5), visceral adipose tissue (slope +0.13, p=1.7e-6), breast mammary tissue (slope +0.11, p=2.3e-6), cultured fibroblasts (slope +0.11, p=6.0e-5), subcutaneous adipose tissue (slope +0.10, p=3.3e-5), and tibial artery (slope +0.09, p=3.2e-7) GTEx Portal
  • TRIM33 expression (decreased in testis and whole blood): The ALT allele is associated with reduced TRIM33 expression in testis (slope -0.12, p=2.1e-5) and whole blood (slope -0.08, p=5.1e-5) GTEx Portal

Evidence quality The height association is drawn from one of the largest human genetic studies ever conducted (up to 5,380,080 participants across 281 studies), which achieved near-saturation of common-variant discovery for European-ancestry populations. The 12,111 identified SNPs collectively explain approximately 40% of height variance in European-ancestry samples (approximately 45% using all HapMap 3 SNPs); in non-European ancestry groups this figure drops to approximately 10-20% (14-24% with HapMap 3 SNPs), a gap attributed to differences in linkage disequilibrium patterns (the tendency for nearby genetic variants to be inherited together as a block) and allele frequencies rather than fundamentally different biology. No individual p-value or effect size for rs11589568 specifically appears in the available study text; the quoted variance figures refer to the collective 12,111-SNP set. The GTEx eQTL findings (FDR < 0.05, n=953 donors) reach statistical significance in each listed tissue but reflect gene-expression mechanisms rather than clinical outcomes.

Tissue-specific expression effects

  • TRIM33: The ALT allele is associated with increased expression in adrenal gland, visceral and subcutaneous adipose tissue, cultured fibroblasts, breast mammary tissue, and tibial artery; the same allele is associated with reduced expression in testis and whole blood GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs11589568?

rs11589568 is a common single-nucleotide polymorphism (a position in the genome where people carry one of two different DNA letters) located near the TRIM33 gene. It has been identified as one of 12,111 common variants significantly associated with adult height, and it also influences TRIM33 gene expression across multiple tissues.

Is rs11589568 linked to height?

Yes. A genome-wide association study of more than 5.4 million individuals identified rs11589568 as one of 12,111 common variants significantly associated with adult height. Together, these variants explain approximately 40% of height variation in people of European ancestry.

How does rs11589568 affect TRIM33 gene expression?

GTEx v11 data show that one version of rs11589568 is associated with increased TRIM33 expression in adrenal gland, adipose tissue, breast tissue, fibroblasts, and tibial artery, but with reduced expression in testis and whole blood. This tissue-specific pattern means the variant has opposite directional effects depending on which tissue is examined.

Does rs11589568 affect people of all ancestries equally for height?

No. The variant set that includes rs11589568 explains approximately 40% of height variance in European-ancestry populations but only about 10-20% in other ancestry groups. Researchers attribute this difference to variation in how nearby genetic variants are linked together (linkage disequilibrium) and how common each variant is across populations, not to fundamentally different biology.

What does it mean that rs11589568 is a cis-eQTL for TRIM33?

A cis-eQTL is a genetic variant that is statistically linked to how much a nearby gene is expressed - essentially, how actively cells are reading and using that gene. rs11589568 being a cis-eQTL for TRIM33 means the two versions of this variant are associated with different amounts of TRIM33 gene activity in tissues near its chromosomal location.