rs11061620 (ERC1): Diverticular Disease Risk

Key takeaways

• rs11061620 is one of 150 newly mapped diverticular disease risk variants found in a study of over 724,000 people.
• A polygenic score including this variant predicts diverticular disease risk, with the top 20% of scorers facing about 3.6 times the average risk.
• This variant has opposite effects on ERC1 gene activity in brain and adrenal tissue versus fat and skin tissue.
• The GWAS linked gut nerve and muscle cell types to diverticular disease development, reinforcing gut-brain connections in intestinal health.

What the research says A genome-wide association study (GWAS - a large-scale scan comparing genetic variants across thousands to millions of individuals) of 724,372 people across multiple biobanks identified rs11061620 as one of 150 genome-wide significant risk variants for diverticular disease (DivD), a condition where small sac-like pouches form in the wall of the intestine. Of those 150 variants, 102 were newly reported at the time of publication. Follow-up analyses implicated gut myocytes (muscle cells of the gut wall), mesothelial and stromal cells, and enteric neurons and glia (the nerve cells forming the gut's own nervous system) in DivD development, and pointed to colon structure, gut motility, gastrointestinal mucus production, and ionic homeostasis (the balance of electrically charged particles inside and outside cells) as likely disease mechanisms.

Reported associations

• Diverticular disease of intestine: identified as one of 150 genome-wide significant risk variants in a GWAS of 724,372 individuals; a polygenic score incorporating all 150 variants achieved an area under the curve (AUC - a measure of prediction accuracy, where 1.0 is perfect) of 0.688 (95% CI: 0.645-0.732), with individuals in the top 20% of scores facing approximately 3.6-fold higher risk compared with the remaining 80%.

Evidence quality The diverticular disease association is derived from a large multi-biobank GWAS (n=724,372), providing substantial statistical power. A total of 150 genome-wide significant variants were identified, 102 of which were newly discovered. Per-variant effect sizes specific to rs11061620 were not reported in the available study text. The polygenic score integrating all 150 variants achieved an AUC of 0.688 (95% CI: 0.645-0.732), reflecting modest-to-moderate predictive accuracy at the population level. No independent replication data for this specific locus were described in the available text. As one of 102 newly reported variants, the evidence for rs11061620's individual contribution to DivD risk remains preliminary.

Tissue-specific expression effects

• ERC1: the alternate allele is associated with increased expression in the brain anterior cingulate cortex, EBV-transformed lymphocytes (an immune-derived cell line used in research), and adrenal gland; reduced expression is observed in cultured fibroblasts, non-sun-exposed suprapubic skin, and subcutaneous adipose tissue GTEx Portal
• ENSG00000250132: the alternate allele is associated with increased expression in tibial nerve and sun-exposed lower leg skin GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.