Migraine LDSC
# LDSC
I applied Linkage Disequilibrium Score Regression1 to the Million Veterans Program2 migraine GWAS. The aim was to estimate heritability and look for signs of stratification and confounding.
The results are below:
| Parameter | Value |
|---|---|
| h2_liab | 0.1005 |
| h2_liab_se | 0.00716 |
| Lambda_gc | 1.3 |
| Mean_chi2 | 1.301 |
| Intercept | 1.107 |
| Intercept_se | 0.007703 |
| Ratio | 0.3561 |
| Ratio_se | 0.0256 |
A heritability of 0.1005 is low-to-moderate.
However, an attenuation ratio of 0.3561 is quite high, suggesting possible confounding by population stratification. This suggests we should be wary of results generated from analysis of these summary statistics. While LDSC-based methods are likely trustworthy, since they model and remove the stratification component, non-LDSC methods may be less trustworthy and could produce misleading results.
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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. ↩