LDSC
Linkage Disequilibrium Score Regression1 was applied to the DECODE meta-GWAS of seronegative rheumatoid arthritis2. The aim was to estimate heritability and look for signs of stratification and confounding.
The results are below:
| Parameter | Value |
|---|---|
| h2_liab | 0.04988 |
| h2_liab_se | 0.01124 |
| Lambda_gc | 1.097 |
| Mean_chi2 | 1.104 |
| Intercept | 1.031 |
| Intercept_se | 0.008046 |
| Ratio | 0.2984 |
| Ratio_se | 0.07728 |
The liability scale heritability is around 0.05, approximately half the liability scale heritability of seropositive RA. Note however, that this finding is dependent on our estimates of the population prevalence of the two types of RA.
The relatively low intercept suggests a relatively low risk of confounding by population stratification.
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Brendan K Bulik-Sullivan, Po-Ru Loh, Hilary K Finucane, Stephan Ripke, Jian Yang, Nick Patterson, Mark J Daly, Alkes L Price, and Benjamin M Neale. LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nature Genetics, 47(3):291–295, 2015. URL: https://pmc.ncbi.nlm.nih.gov/articles/PMC4495769/. ↩
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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. ↩