rs11084786 (LINC01801): Serum Urate and ZNF181 eQTL

Key takeaways

• This variant reduces ZNF181 gene activity in eight different tissue types, including brain, thyroid, fat tissue, and artery
• rs11084786 near LINC01801 was studied in a genome-wide scan of blood uric acid levels across more than 42,000 people
• The uric acid study tested whether body weight (BMI) modifies genetic effects on urate, finding evidence of BMI-dependent differences for several loci
• Evidence for a confirmed clinical health effect of this specific variant remains preliminary based on available data

What the research says A genome-wide association study (GWAS, a method that systematically scans the genome for variants linked to a measurable trait) pooling 22 population cohorts of European descent and up to 42,569 participants tested whether common genetic variants affecting serum urate (uric acid dissolved in the blood) are modulated by body mass index (BMI, a weight-to-height ratio used as a body-fatness proxy). Participants were classified as lean (BMI below 25), overweight (BMI 25 to 30), or obese (BMI above 30), and both stratified genome-wide analyses and interaction-term regression models were applied to identify loci whose urate-associated effects differ across BMI categories. Separately, GTEx v11 tissue-expression data (953 donors, cis-window, FDR below 0.05) identify rs11084786 as an eQTL (expression quantitative trait locus, a variant that influences how actively a gene is transcribed in a given tissue) for ZNF181 (zinc finger protein 181), with the alternate allele consistently associated with reduced ZNF181 expression across eight tissues at p-values ranging from approximately 10^-15 to 10^-32 GTEx Portal.

Reported associations

• Serum urate levels: rs11084786, located near LINC01801 (a long intergenic non-coding RNA, meaning a genomic segment that is transcribed but does not encode a protein), was included in a large multi-cohort GWAS examining genetic associations with serum urate and their potential modulation by BMI, involving up to 42,569 participants across 22 European-descent cohorts
• ZNF181 expression (multiple tissues): the alternate allele is associated with reduced expression of ZNF181 in eight tested tissue types at FDR below 0.05, with p-values indicating a strong and consistent molecular signal GTEx Portal

Evidence quality The serum urate GWAS drew on up to 42,569 participants from 22 cohorts of European descent, which represents a sizable discovery sample. The study design included both BMI-stratified GWAS meta-analyses and linear regression interaction tests, with an independent replication set available for selected top loci. However, the provided study text does not report a specific p-value, odds ratio, or effect size for rs11084786 itself, and no confirmed independent replication of an association at this specific locus is described in the available materials. The evidence linking this variant to serum urate levels should therefore be considered preliminary. For the molecular signal, GTEx eQTL data from 953 donors show that ZNF181 expression is reduced in eight tissue types at stringent FDR thresholds, with the most significant effects observed in thyroid (p approximately 10^-31), tibial nerve (p approximately 10^-32), and visceral adipose tissue (p approximately 10^-32) GTEx Portal, representing consistent cross-tissue replication of the eQTL effect. No conflicting findings are present in the provided sources.

Tissue-specific expression effects

• ZNF181: the alternate allele of rs11084786 is associated with reduced expression of ZNF181 in cervical spinal cord, cerebellar hemisphere, thyroid, visceral adipose tissue (omentum), tibial nerve, sigmoid colon, subcutaneous adipose tissue, and tibial artery; this reduced-expression pattern is statistically robust across all eight tissues at FDR below 0.05, with highly significant p-values in each tissue type GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.