Extended Data Fig. 3: Relative efficiency of HDL against LDSC under different model setups when 10% SNPs with 5% > MAF > 1% are causal.
From: High-definition likelihood inference of genetic correlations across human complex traits
52,914 out of 221,620 array SNPs with 5% > MAF > 1% were randomly selected as causal variants. 100 pairs of traits were generated, where true genetic correlation and phenotypic correlation are 0.5. The true phenotypes of trait i is generated from model \({\mathbf{y}}_i = \mathop {\sum}\nolimits_{k = 1}^M {{\mathbf{X}}_{ik}\beta _{ik} + \epsilon_i}\), where \({\mathbf{X}}_{ik} = ({\mathbf{Z}}_{ik} - 2p_k1)[2p_k(1 - p_k)]^{\alpha /2}\); Zik are the original genotypes of SNP k for trait i; pk is the MAF of SNP k; M is the number of causal variants. Four scenarios were simulated: (1) α = −1, and the marginal distribution of βik is \(N(0,h_i^2/M)\); (2) α = −1, and the marginal distribution of βik is \(N(0,w_kh_i^2/M)\), where wk is the LDAK weight of SNP k which is inversely proportional to its LD score; (3) α =−0.25, and the marginal distribution of βik is \(N(0,h_i^2/M)\) and (4) α =−0.25, and the marginal distribution of βik is \(N(0,w_kh_i^2/M)\). After βi were generated, they were rescaled by multiplying the same constant so that the true heritabilities were 0.5 for both traits. The 307,519 array SNPs of ~336,000 UKBB genomic British individuals were used to simulate true phenotypes and to compute LD matrix for both HDL and LDSC. The P-values are from Levene’s test for variance heterogeneity. Inside each box, the line indicates the median value, the central box indicates the interquartile range (IQR), and whiskers extend up to 1.5 times the IQR.
