Expressive

rs10780783 (LINC02834/GAS1): Orofacial Cleft Subtypes

Key takeaways

  • This variant near LINC02834 and GAS1 has been studied in connection with orofacial cleft subtypes.
  • Bilateral cleft lip and unilateral cleft lip show partly different genetic patterns, with 44% of suggestive signals diverging between the two subtypes.
  • GTEx data link this variant to reduced activity of LINC02834 in non-sun-exposed skin.
  • A neighboring gene (ENSG00000297364) shows increased activity in fat and esophageal tissue linked to this variant.
  • Evidence is preliminary; specific results for this variant individually are not detailed in the available study text, and the bilateral cleft sample was small (n = 44).

Key takeaways

  • This variant near LINC02834 (a long intergenic non-coding RNA) and GAS1 has been studied in connection with orofacial cleft subtypes - structural birth defects affecting the lip or roof of the mouth.
  • Research suggests bilateral cleft lip (both sides) and unilateral cleft lip (one side) have partly distinct genetic roots, with 44% of suggestive signals diverging in effect between the two subtypes.
  • GTEx data link this variant to reduced expression of LINC02834 in non-sun-exposed skin.
  • A neighboring gene (ENSG00000297364) at this locus shows increased expression in esophageal and fat tissue when this variant is present.
  • Evidence is preliminary; specific effect sizes for rs10780783 individually are not reported in the available study text, and the bilateral cleft lip group was small (n = 44).

What the research says A genome-wide study of orofacial cleft subtypes enrolled 44 individuals with bilateral cleft lip (BCL, cleft on both sides of the lip), 434 with unilateral cleft lip (UCL, one side), 530 with bilateral cleft lip and palate, 1,123 with unilateral cleft lip and palate, and 1,626 unrelated controls from 18 international sites across 13 countries, finding that 44.03% of suggestive genetic signals differed in effect between BCL and UCL, indicating these subtypes have partly distinct genetic causes. A modifier locus near PAX1 on chromosome 20p11 (p = 7.53 x 10^-9) was also identified in the same study as increasing the odds of BCL over UCL, replicating in an independent cohort (p = 0.0018) with no effect in bilateral cleft lip and palate (p > 0.05). GTEx eQTL data - which quantify how a variant changes nearby gene activity - show that the ALT allele of rs10780783 is associated with reduced expression of LINC02834 in non-sun-exposed skin and with increased expression of ENSG00000297364 in esophageal and adipose (fat) tissue GTEx Portal.

Reported associations

  • Bilateral vs. unilateral cleft lip (orofacial cleft subtype): A genome-wide study found the genetic architecture of BCL to be partly distinct from UCL, with 44.03% of suggestive loci showing divergent effects between the two subtypes across a sample of 44 BCL cases, 434 UCL cases, and 1,626 controls.
  • Normal nasal shape: A modifier locus near PAX1 on chromosome 20p11 - identified in the same orofacial cleft study - was also associated with normal variation in human nasal morphology, illustrating how cleft-related genetic regions can overlap with facial shape traits more broadly.

Evidence quality The orofacial cleft study drew samples from 18 international sites across 13 countries and used a mixed-model approach to account for population structure. The bilateral cleft lip subgroup was small (n = 44), which limits statistical power for this relatively rare phenotype. The PAX1 modifier locus achieved genome-wide significance (p = 7.53 x 10^-9) and replicated in an independent cohort (p = 0.0018), and showed no detectable effect in bilateral cleft lip and palate (p > 0.05), suggesting specificity to the BCL vs. UCL distinction. The provided study text does not report a specific p-value or effect size for rs10780783 individually, so its contribution within this locus cannot be quantified from the available excerpt. GTEx expression data are from 953 donors in GTEx v11 with a false discovery rate below 5% (FDR < 0.05); these eQTL findings describe gene regulation patterns and are not direct evidence of clinical outcomes.

Tissue-specific expression effects

  • ENSG00000288575: The ALT allele is linked to reduced expression in non-sun-exposed skin (suprapubic region, p = 4.5 x 10^-15) and sun-exposed skin (lower leg, p = 3.6 x 10^-11) GTEx Portal.
  • LINC02834: The ALT allele is linked to reduced expression in non-sun-exposed skin (suprapubic region, p = 1.5 x 10^-7) GTEx Portal.
  • ENSG00000297364: The ALT allele is linked to increased expression in esophageal tissue at the gastroesophageal junction (p = 1.6 x 10^-5), visceral adipose tissue - fat surrounding internal organs (p = 4.1 x 10^-5) - and subcutaneous adipose tissue - fat just beneath the skin (p = 5.0 x 10^-5) GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs10780783?

rs10780783 is a single-letter DNA variant located near the LINC02834 and GAS1 genes. It has been studied in the context of orofacial cleft subtypes and shows effects on gene expression in skin and fat tissue in GTEx data.

Is rs10780783 associated with cleft lip?

A genome-wide study of orofacial cleft subtypes examined this locus in the context of bilateral versus unilateral cleft lip. The evidence is preliminary, and the small number of bilateral cleft lip cases (n = 44) in the study limits the strength of any conclusions.

What does LINC02834 do?

LINC02834 stands for Long Intergenic Non-Coding RNA 02834, a gene product that does not produce protein but can influence how other genes are regulated. GTEx data show that this variant is associated with reduced LINC02834 expression in non-sun-exposed skin tissue.

What tissues does rs10780783 affect according to GTEx?

GTEx data show reduced expression of LINC02834 and ENSG00000288575 in skin (both sun-exposed and non-sun-exposed types), and increased expression of ENSG00000297364 in esophageal tissue and two types of fat tissue (visceral and subcutaneous adipose).

What is the difference between bilateral and unilateral cleft lip?

Bilateral cleft lip affects both sides of the lip, while unilateral cleft lip affects only one side. Research suggests these two forms may have partly different genetic causes, as evidenced by divergent genetic signals at roughly 44% of suggestive loci in a genome-wide study.