LDSC Analysis
I applied Linkage Disequilibrium Score Regression1 to the Million Veterans LDL GWAS of Verma et al.1 to estimate heritability and look for signs of population stratification or confounding.
The results are shown in the table below:
| Parameter | Value |
|---|---|
| h2_liab | 0.1145 |
| h2_liab_se | 0.01864 |
| Lambda_gc | 1.983 |
| Mean_chi2 | 2.448 |
| Intercept | 1.586 |
| Intercept_se | 0.01802 |
| Ratio | 0.405 |
| Ratio_se | 0.01245 |
The heritability of 0.1145 is low-to-moderate. The LD score regression intercept of 1.586 is large, and indicates possible confounding or population stratification. This finding may be grounds to take any results that build on the Verma et al. summary statistics with a grain of salt. At minimum, we should compare with other LDL GWAS.
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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/. ↩↩