rs1189402 (LINC02490-WDR72): CRP Inflammation

Key takeaways

• rs1189402 is one of 58 genetic markers for C-reactive protein (CRP), a blood test for chronic inflammation, found across a study of over 200,000 people.
• Statistical methods suggest higher CRP levels may be protective against schizophrenia but increase bipolar disorder risk - an intriguing but indirect finding.
• GTEx data show the alternate allele reduces expression of a nearby gene (ENSG00000300550) in testis tissue.
• All 58 CRP-linked variants together account for up to 7.0% of the variation in CRP blood levels.
• This association comes from one large meta-analysis of 88 studies; independent replication for this specific locus is not reported.

What the research says rs1189402, in the LINC02490-WDR72 region, was identified as one of 58 genome-wide significant loci for circulating CRP in a meta-analysis of 204,402 European individuals drawn from 88 cohort studies. The 58 lead variants collectively explained up to 7.0% of the variance in CRP, with gene sets organized into two correlated clusters - one dominated by immune pathways and the other by liver metabolic pathways. Mendelian randomization using these CRP-associated variants found evidence for a causal protective effect of CRP on schizophrenia and a causal risk-increasing effect on bipolar disorder.

Reported associations

• C-reactive protein levels: rs1189402 is one of 58 genome-wide significant loci for circulating CRP in a meta-analysis of 204,402 Europeans across 88 studies; the 58 lead variants jointly explain up to 7.0% of CRP variance.
• Schizophrenia (Mendelian randomization): Mendelian randomization using CRP-associated loci found evidence for a causal protective effect of higher CRP on schizophrenia risk.
• Bipolar disorder (Mendelian randomization): The same Mendelian randomization analysis found a risk-increasing causal relationship between CRP and bipolar disorder.

Evidence quality The CRP association for this locus comes from a well-powered meta-analysis (n=204,402 Europeans, 88 contributing studies) using both HapMap and 1000 Genomes imputed data. However, the available study does not report a variant-specific effect size for rs1189402 alone - only the combined figure of up to 7.0% variance explained across all 58 loci. After adjustment for body mass index, associations at all but three of the 58 loci remained significant; the study does not specify which loci were the three exceptions. The Mendelian randomization findings for schizophrenia and bipolar disorder rest on the aggregate set of CRP loci rather than on this variant specifically, and are inferential statistical findings rather than direct causal measurements. No replication data specific to the LINC02490-WDR72 locus are described. The study population is exclusively of European ancestry, which limits generalizability to other populations.

Tissue-specific expression effects

• ENSG00000300550: Reduced expression in testis tissue associated with the alternate allele, based on GTEx v11 data across 953 donors (p=7.9e-6). GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.