Expressive

rs11177752 (LRRC10-BEST3): Height GWAS Locus

Key takeaways

  • rs11177752 is in the LRRC10-BEST3 genomic region, identified in a 5.4 million-person height study - the largest of its kind.
  • The study found 12,111 height-associated variants that together explain roughly 40% of height variation in European ancestry populations.
  • This variant is also linked to gene activity changes in the heart, testis, thyroid, blood, and skin per GTEx tissue data.
  • Height prediction accuracy drops to roughly 10-20% in non-European ancestry populations compared to approximately 40% in European ancestry populations.

Key takeaways

  • rs11177752 is in the LRRC10-BEST3 genomic region, identified in the largest genome-wide height study to date, covering more than 5.4 million people across five ancestry groups.
  • The study found 12,111 independent height-associated variants that together explain roughly 40% of height variation in European ancestry populations.
  • GTEx tissue data show this variant is linked to changes in gene activity across multiple organs, including heart, testis, thyroid, blood, and skin.
  • Prediction accuracy for height using variants like this one drops to roughly 10-20% in non-European ancestry populations.

What the research says rs11177752 falls in a genomic segment annotated to the LRRC10 (leucine-rich repeat containing protein 10) and BEST3 (bestrophin 3) genes, and was identified in a multi-ancestry genome-wide association study (GWAS) of adult height covering up to 5,380,080 individuals from 281 studies across European, East Asian, Hispanic, African, and South Asian ancestry groups. That study mapped 12,111 independent height-associated variants into 7,209 non-overlapping genomic segments averaging roughly 90 kb each and covering about 21% of the genome, with those variants explaining approximately 40% of height variation in European ancestry populations (rising to approximately 45% when all HapMap 3 panel SNPs were included). Tissue expression data from GTEx show that this locus is linked to altered activity of at least five nearby genes, LRRC10, FRS2, RAB3IP, LYZ, and CCT2, spanning tissues including testis, heart, thyroid, blood, and skin. GTEx Portal

Reported associations

  • Adult height: rs11177752 is among 12,111 independent variants significantly associated with adult height in a GWAS of more than 5.4 million individuals; the available study text does not report a per-allele effect size specific to this variant.

Evidence quality The height GWAS underlying this entry is one of the largest genetic studies ever conducted, with more than 5.4 million participants from five major ancestry groups. Its authors report that the 12,111 identified variants largely saturate the common-variant heritability of height in European ancestry populations, a substantial advance over earlier work that found up to 3,290 associations using approximately 700,000 individuals. No per-variant effect size, p-value, or allele frequency specific to rs11177752 is reported in the study excerpt provided, so the individual contribution of this variant cannot be precisely quantified from the available data. Prediction accuracy drops to roughly 10-20% in non-European ancestry populations compared to approximately 40% in European ancestry, with the study authors attributing this gap to differences in linkage disequilibrium patterns and allele frequencies across populations. No conflicting association findings were identified in the materials provided.

Tissue-specific expression effects

  • LRRC10: increased expression in testis and reduced expression in heart atrial appendage GTEx Portal
  • FRS2: reduced expression in thyroid and increased expression in cultured fibroblasts GTEx Portal
  • RAB3IP: reduced expression in heart atrial appendage GTEx Portal
  • LYZ: increased expression in whole blood GTEx Portal
  • CCT2: increased expression in testis and in sun-exposed lower-leg skin GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs11177752?

rs11177752 is a common DNA variant (single-nucleotide polymorphism) located near the LRRC10 and BEST3 genes. It was identified as one of 12,111 variants significantly associated with adult human height in a large multi-ancestry genome-wide study of more than 5.4 million people.

What genes are near rs11177752?

rs11177752 is annotated to two nearby genes: LRRC10, which encodes a leucine-rich repeat containing protein, and BEST3, which encodes bestrophin 3, a calcium-sensitive chloride channel protein.

Is rs11177752 associated with height?

Yes. It was captured in a genome-wide association study of more than 5.4 million individuals as one of 12,111 variants significantly associated with adult height. A specific per-allele effect size for this individual variant was not reported in the available study data.

Does rs11177752 affect gene expression in tissues?

GTEx tissue data show that this locus is linked to altered expression of LRRC10 (higher in testis, lower in heart atrial appendage), FRS2 (lower in thyroid, higher in cultured fibroblasts), RAB3IP (lower in heart atrial appendage), LYZ (higher in whole blood), and CCT2 (higher in testis and sun-exposed lower-leg skin).

Why is height prediction less accurate in non-European populations?

The underlying study found that prediction accuracy drops to roughly 10-20% in non-European ancestry populations compared to about 40% in European ancestry populations. The researchers attributed this difference to variation in linkage disequilibrium patterns and allele frequencies across populations.