LDSC (Said et al, C Reactive Protein)
I applied Linkage Disequilibrium Score Regression1 to the CRP GWAS of Said et al.2 to estimate heritability and look for signs of population stratification or confounding.
The results are in the table below:
| Parameter | Value |
|---|---|
| h2_liab | 0.1683 |
| h2_liab_se | 0.03026 |
| Lambda_gc | 1.72 |
| Mean_chi2 | 2.813 |
| Intercept | 1.065 |
| Intercept_se | 0.01747 |
| Ratio | 0.0357 |
| Ratio_se | 0.009638 |
A heritability of 0.1683 is low-to-moderate, while a LDSC intercept 1.065 suggested a well-structured GWAS without obvious confounding or stratification. The high mean chi-squared (2.813) indicates a highly polygenic trait.
To illustrate the fit of the LDSC model to the data, I also generated the LDSC diagnostic plot below.
LDSC diagnostic plot. Genetic variants are binned by LD Score. For each bin, we plot the mean LD score of variants in the bin (x axis) against Wald chi squared statistic (y axis 1) and scaled Wald chi squared statistic (y axis 2). Each plotted bin includes error bars indicating the standard error of bin chi squared mean. We also plot the LDSC regression line (solid) and the line corresponding to chi squared =1 (dashed). If the LDSC model fits the data perfectly, we should expect that the intercept of the regression line is at chi squared=1
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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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Anurag Verma, Jennifer E Huffman, Alex Rodriguez, Mitchell Conery, Molei Liu, Yuk-Lam Ho, Youngdae Kim, David A Heise, Lindsay Guare, Vidul Ayakulangara Panickan, and others. Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. Science, 385(6706):eadj1182, 2024. URL: https://www.science.org/doi/10.1126/science.adj1182. ↩