Skip to content

LDSC Analysis

I applied Linkage Disequilibrium Score Regression1 to the non-23-and-me European subset of the adult height GWAS of Yengo et al.2 to estimate heritability and look for signs of population stratification or confounding.

The results are below:

Parameter Value
h2_liab 0.4314
h2_liab_se 0.02148
Lambda_gc 5.191
Mean_chi2 15.38
Intercept 2.429
Intercept_se 0.05703
Ratio 0.09943
Ratio_se 0.003967

A SNP heritability of approximately 43% is consistent with estimates from other sources.

An LD-score regression intercept of 2.429 and a genomic control \(\lambda\) of 5.191 may seem high. Note however, that height is a highly polygenic trait, and the Yengo GWAS has a very large sample size. This is reflected in the very large mean \(\chi^2\) (15.38). In such a circumstances, the best measure of degree of potential stratification/ confounding is the attenuation ratio, which is calculated as

\[ \frac{\text{intercept} -1}{\chi^2_{\text{mean}} -1}. \]

Here the attenuation ratio is 0.09943, which suggests an acceptably low level of stratification.

  1. 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/. ↩

  2. Loïc Yengo, Sailaja Vedantam, Eirini Marouli, Julia Sidorenko, Eric Bartell, Saori Sakaue, Marielisa Graff, Anders U Eliasen, Yunxuan Jiang, Sridharan Raghavan, and others. A saturated map of common genetic variants associated with human height. Nature, 610(7933):704–712, 2022. URL: https://www.nature.com/articles/s41586-022-05275-y. ↩