rs11204 (CALD1): Orbital Telorism Genetic Variant

Key takeaways

• rs11204 is one of 56 genomic loci significantly associated with orbital telorism (the measured distance between the eyes) in a genome-wide study of more than 34,000 adults.
• Genes near these 56 loci are nearly 5 times more enriched than expected for genes already known to cause rare Mendelian (single-gene) eye-spacing disorders, supporting biological relevance.
• Orbital telorism is estimated to be 39% to 76% heritable, meaning genetic variation accounts for a substantial share of differences in eye spacing between people.
• The study's primary findings in 34,130 individuals were independently replicated in a second sample of 10,115 individuals.
• GTEx data show that the alternative allele at this locus is associated with changed expression of nearby genes in artery, fat, lung, and skeletal muscle tissues.

What the research says A genome-wide association study (GWAS) - a method that scans the genome across hundreds of thousands of genetic markers to find those statistically linked to a trait - in 34,130 European adults identified 56 significantly associated loci (P < 5 x 10^-8) for orbital telorism, the distance between the centers of the eyeballs as measured on MRI. Of the 56 loci, 46 were novel for facial morphology. Findings replicated in an independent sample of 10,115 individuals using telorism-related horizontal facial distance measures, and genes near the 56 loci showed a 4.9-fold enrichment for genes already known to cause inherited hypo- or hypertelorism disorders, supporting their biological plausibility.

Reported associations

• Orbital telorism (interocular distance): rs11204 is among 56 loci genome-wide significantly associated (P < 5 x 10^-8) with the MRI-measured distance between the eyes in 34,130 European adults, with replication in 10,115 additional individuals.

Evidence quality The GWAS was conducted in 34,130 European adults and replicated in 10,115 individuals from an independent sample, providing moderate replication support. Heritability of orbital telorism was estimated at 76% (standard error 12%) by a family-based method (N = 364) and 39% (standard error 2.4%) by a SNP-based method (N = 34,130). The 4.9-fold enrichment of nearby genes for known Mendelian eye-spacing disorder genes adds biological plausibility. The available study text does not report an individual effect size (such as a beta coefficient or odds ratio) for rs11204 specifically, limiting direct quantification of its contribution. The study sample is restricted to European ancestry individuals, which may limit generalizability to other populations.

Tissue-specific expression effects

• ENSG00000287733: The alternative allele at rs11204 is associated with increased expression in aortic artery, visceral adipose (belly fat), subcutaneous adipose (fat just under the skin), lung, and skeletal muscle, and with decreased expression in testis GTEx Portal.
• ENSG00000272941: The alternative allele is associated with increased expression in EBV-transformed lymphocytes (a laboratory white-blood-cell-derived cell line used in genetic research) GTEx Portal.
• CYREN: The alternative allele is associated with increased expression in EBV-transformed lymphocytes GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.