rs10987803 (EEIG1-NAIF1): Gout, Lipids, and PIP5KL1
Key takeaways
- rs10987803 was identified in one of the largest gout genetics studies to date, covering 2.6 million people including 120,295 with the disease.
- The same variant also appeared in a large multi-ancestry blood lipid study covering approximately 1.65 million individuals across five ancestry groups.
- In GTEx data from 953 donors, carrying the ALT allele is linked to increased PIP5KL1 expression in coronary arteries, aorta, adipose tissue, and other tissues.
- A cross-population atlas of 220 phenotypes also reported associations at this locus across Japanese and European populations.
Key takeaways
- rs10987803 was identified in one of the largest gout genetics studies to date, covering 2.6 million people including 120,295 with the disease.
- The same variant also appeared in a large multi-ancestry blood lipid study covering approximately 1.65 million individuals across five ancestry groups.
- In GTEx data from 953 donors, carrying the ALT allele is linked to increased PIP5KL1 expression in coronary arteries, aorta, adipose tissue, and other tissues.
- A cross-population atlas of 220 phenotypes also reported associations at this locus across Japanese and European populations.
What the research says This variant at the EEIG1 - NAIF1 locus was identified in a large GWAS (genome-wide association study, a method that scans millions of genetic variants across the genome simultaneously) of gout and urate levels covering 2.6 million participants, including 120,295 people with gout, which detected 377 associated loci (genomic regions) and 410 genetically independent signals including 149 previously unreported loci PMID 38049663. The locus also appeared in a multi-ancestry blood lipid GWAS of approximately 1.65 million individuals from five ancestry groups (Admixed African, East Asian, European, Hispanic, and South Asian), which found 941 lipid-associated loci including 355 novel ones PMID 34887591. A cross-population phenotype atlas of 220 traits in BioBank Japan, meta-analyzed with the UK Biobank and FinnGen (combined n up to 628,000), which identified approximately 5,000 new loci, also reported findings at this locus PMID 34385711.
Reported associations
- Gout and urate levels: This variant was among 377 loci identified in a genome-wide study of 2.6 million participants including 120,295 people with gout; the study examined molecular mechanisms in the inflammatory biology of gout, including genes involved in epigenetic remodeling and NLRP3 (NOD-like receptor protein 3) inflammasome regulation PMID 38049663.
- Blood lipid levels: The locus was identified in a multi-ancestry GWAS of approximately 1.65 million individuals examining LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), triglycerides, total cholesterol, and non-HDL-C PMID 34887591.
- Multiple phenotypes across populations: The locus appeared in a cross-population atlas of 220 phenotypes including diseases, biomarkers, and medication use, conducted across Japanese and European populations PMID 34385711.
Evidence quality All three reporting studies are large-scale GWAS meta-analyses with sample sizes ranging from hundreds of thousands to 2.6 million, substantially reducing the probability of false-positive associations. The gout study enrolled 2.6 million participants across multiple ancestries and used genome-wide significance thresholds, finding 377 associated loci including 149 previously unreported PMID 38049663. The lipid study included 350,000 non-European participants across five ancestry groups, providing cross-ancestry replication for the 941 loci it identified PMID 34887591. The cross-population atlas used meta-analyses across BioBank Japan, UK Biobank, and FinnGen (n up to 628,000), identifying approximately 5,000 new loci PMID 34385711. Specific p-values, odds ratios, or beta coefficients for rs10987803 itself are not reported in the provided study excerpts, so the strength and direction of its effect on individual traits cannot be quantified here. No conflicting findings between the three studies were noted in the provided evidence.
Tissue-specific expression effects
- PIP5KL1: The ALT allele of rs10987803 is associated with increased expression of PIP5KL1 across eight tissues, with log2-normalized effect slopes ranging from +0.75 to +0.93. The largest slope was observed in coronary artery (+0.93, p=3.8e-11) and the strongest statistical significance in subcutaneous adipose tissue (+0.88, p=1.5e-24). Other tissues with increased expression include the esophageal gastroesophageal junction (+0.90, p=3.2e-13), esophageal muscularis (+0.87, p=5.4e-21), tibial nerve (+0.84, p=1.9e-23), visceral adipose tissue or omentum (+0.83, p=2.8e-17), aorta (+0.82, p=3.2e-16), and tibial artery (+0.75, p=1.7e-20). All eight tissues show the same direction of effect. These eQTL (expression quantitative trait locus) findings describe a potential biological mechanism and do not directly indicate clinical outcomes GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs10987803?
rs10987803 is a genetic variant at the EEIG1 - NAIF1 locus. Large genetic studies have linked it to gout, urate levels, and blood lipid traits, and GTEx data from 953 tissue donors shows it is associated with higher expression of a nearby gene called PIP5KL1 in multiple tissues including coronary arteries and fat tissue.
Is rs10987803 associated with gout?
This variant was identified in a genome-wide association study that enrolled 2.6 million people, including over 120,000 with gout. The study detected 377 genomic regions linked to gout or urate levels and focused on the inflammatory biology of gout, including the NLRP3 inflammasome pathway.
What are EEIG1 and NAIF1?
EEIG1 and NAIF1 are the two genes that give this locus its name. The variant rs10987803 sits in the genomic region near these two genes. Notably, the GTEx expression data for this variant shows effects on a third nearby gene, PIP5KL1, rather than on EEIG1 or NAIF1 directly.
What is PIP5KL1 and why does rs10987803 affect its expression?
PIP5KL1 is a gene located near the EEIG1 - NAIF1 locus. GTEx data from 953 tissue donors shows that people carrying the ALT allele of rs10987803 tend to have higher PIP5KL1 expression in eight tissues, including coronary artery, aorta, subcutaneous and visceral fat, and tibial nerve. This is a tissue-expression association and does not directly indicate a clinical outcome.
Is rs10987803 linked to blood cholesterol or triglycerides?
This variant appeared in a large multi-ancestry genetic study of blood lipid levels covering about 1.65 million individuals from five ancestry groups, which examined LDL cholesterol, HDL cholesterol, triglycerides, total cholesterol, and non-HDL cholesterol across 941 lipid-associated genomic regions. Specific effect sizes for rs10987803 on individual lipid measures are not available from the provided study summaries.