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S-LDSC

I applied stratified linkage disequilibrium score regression (S-LDSC)1 to summary statistics from DECODE's meta-GWAS of seronegative rheumatoid arthritis (RA)2.

Reference Data Sources

I used the standard reference datasets prepared by the authors of the S-LDSC method.

Results

Interestingly, and in contrast to the analogous analysis for seropositive RA, there we no significant tissue or cell types. It is unclear what this means. It could reflect either a mechanistic heterogeneity of patients assigned the diagnostic label "seronegative RA", or could indicate that the key cell type underlying the pathomechanism of seronegative RA is not present in any of the reference datasets I used.

  1. Hilary K Finucane, Yakir A Reshef, Verneri Anttila, Kamil Slowikowski, Alexander Gusev, Andrea Byrnes, Steven Gazal, Po-Ru Loh, Caleb Lareau, Noam Shoresh, and others. Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types. Nature Genetics, 50(4):621–629, 2018. URL: https://pmc.ncbi.nlm.nih.gov/articles/PMC5896795/. ↩

  2. Saedis Saevarsdottir, Lilja Stefansdottir, Patrick Sulem, Gudmar Thorleifsson, Egil Ferkingstad, Gudrun Rutsdottir, Bente Glintborg, Helga Westerlind, Gerdur Grondal, Isabella C Loft, and others. Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset. Annals of the rheumatic diseases, 81(8):1085–1095, 2022. URL: https://www.sciencedirect.com/science/article/pii/S0003496724209766. ↩