Improved Estimation of Phenotypic Correlations Using Summary Association Statistics

Estimating the phenotypic correlations between complex traits and diseases based on their genome-wide association summary statistics has been a useful technique in genetic epidemiology and statistical genetics inference. Two state-of-the-art strategies, Z-score correlation across null-effect single nucleotide polymorphisms (SNPs) and LD score regression intercept, were widely applied to estimate phenotypic correlations. Here, we propose an improved Z-score correlation strategy based on SNPs with low minor allele frequencies (MAFs), and show how this simple strategy can correct the bias generated by the current methods. The low MAF estimator improves phenotypic correlation estimation, thus it is beneficial for methods and applications using phenotypic correlations inferred from summary association statistics.