Expressive

rs10819689 (NAMA): Lupus Risk Variant

Key takeaways

  • rs10819689 in the NAMA locus was investigated as a candidate variant in one of the largest multi-ancestry genetic studies of systemic lupus erythematosus to date
  • The study spanned over 27,500 individuals from European, African American, and Hispanic Amerindian backgrounds
  • Risk allele accumulation across the genome showed a non-linear, accelerating relationship with SLE risk, pointing to a cumulative-hit model of autoimmune susceptibility
  • The alternate allele at this variant is linked to altered gene expression in thyroid and skeletal muscle tissue per GTEx eQTL data
  • No lifestyle or drug-response data are on file for this variant

Key takeaways

  • rs10819689 in the NAMA locus was investigated as a candidate variant in one of the largest multi-ancestry genetic studies of systemic lupus erythematosus (SLE) to date
  • The study spanned over 27,500 individuals from European, African American, and Hispanic Amerindian backgrounds
  • Risk allele accumulation across the genome showed a non-linear, accelerating relationship with SLE risk, pointing to a cumulative-hit model of autoimmune susceptibility
  • The alternate allele at this variant is linked to altered gene expression in thyroid and skeletal muscle tissue per GTEx eQTL data
  • No lifestyle or drug-response data are on file for this variant

What the research says A transancestral Immunochip association study of SLE (Langefeld et al., Nature Communications, 2018) analyzed genotype data from 27,574 individuals of European (EA), African American (AA), and Hispanic Amerindian (HA) ancestry, identifying 24 novel SLE risk loci at genome-wide significance (p < 5 x 10^-8). More than 50% of the identified regions harbored multiple independent association signals, and the risk allele count per individual showed a non-linear, accelerating relationship with SLE risk exceeding what would be expected if loci acted independently - supporting a cumulative-hit hypothesis for autoimmune disease. The study also confirmed and extended prior associations to additional ancestry groups, capturing both ancestry-dependent and ancestry-independent contributions to SLE risk.

Reported associations

  • Systemic lupus erythematosus (SLE): rs10819689 in the NAMA locus was examined within a transancestral Immunochip study of SLE that included 6,748 EA cases and 11,516 controls, 2,970 AA cases and 2,452 controls, and 1,872 HA cases and 2,016 controls. Specific per-variant effect sizes for this variant are not present in the available study excerpt.

Evidence quality The Langefeld et al. (2018) study is among the largest SLE genetic association studies published, drawing on 27,574 participants across three ancestral groups genotyped on the Immunochip platform (196,524 polymorphisms). The analysis applied admixture-adjusted logistic regression; genomic inflation factors (a measure of population stratification) scaled to 1,000 cases and 1,000 controls were approximately 1.03 for EA and AA cohorts and 1.13 for HA, indicating well-controlled ancestry confounding. Tier 1 significance was set at p < 5 x 10^-8, more stringent than standard Bonferroni correction. However, the specific odds ratio or beta coefficient for rs10819689 is not present in the available text, and independent external replication of this specific locus is not documented in the materials provided. Evidence for this variant's individual contribution should therefore be considered preliminary until confirmed in replication samples.

Tissue-specific expression effects

  • ENSG00000287955: The alternate allele at rs10819689 is associated with increased expression of this gene in thyroid tissue, reaching FDR significance in GTEx v11 data (953 donors) GTEx Portal
  • ENSG00000298775: The alternate allele at rs10819689 is associated with reduced expression of this gene in skeletal muscle tissue, reaching FDR significance in GTEx v11 data (953 donors) GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs10819689?

rs10819689 is a single-nucleotide polymorphism (a position in the genome where one DNA letter varies between people) located in the NAMA locus. It has been studied in connection with systemic lupus erythematosus, a chronic autoimmune disease that can affect multiple organs.

Is rs10819689 linked to lupus?

It was investigated in a large transancestral genetic study of SLE involving more than 27,500 people across three ancestries, which identified 24 novel lupus-risk regions at genome-wide significance. Specific effect size data for this individual variant are not available in the published excerpt.

What is the NAMA locus?

The NAMA locus is the genomic region containing rs10819689. Its functional role is not described in the currently available study materials, though GTEx expression data indicate that variation at this locus influences gene activity in thyroid and skeletal muscle tissue.

Which tissues show expression changes linked to rs10819689?

According to GTEx v11 data from 953 donors, the alternate allele at rs10819689 is associated with increased expression of one nearby gene in thyroid tissue and reduced expression of another in skeletal muscle. These are gene-expression associations and do not directly indicate clinical outcomes.

How strong is the evidence for rs10819689?

The supporting study is large (over 27,500 participants across three ancestries) and used stringent statistical thresholds (p < 5 x 10^-8). However, the specific effect size for this variant is not available in the published excerpt, and independent replication for this exact locus is not documented in the provided materials, so the evidence should be considered preliminary.