Comparison of methods for estimating genetic correlation between complex traits using GWAS summary statistics.
Genetic correlation is the correlation of phenotypic effects by genetic variants across the genome on two phenotypes. It is an informative metric to quantify the overall genetic similarity between complex traits, which provides insights into their polygenic genetic architecture. Several methods have been proposed to estimate genetic correlation based on data collected from genome-wide association studies (GWAS). Due to the easy access of GWAS summary statistics and computational efficiency, methods only requiring GWAS summary statistics as input have become more popular than methods utilizing individual-level genotype data. Here, we present a benchmark study for different summary-statistics-based genetic correlation estimation methods through simulation and real data applications. We focus on two major technical challenges in estimating genetic correlation: marker dependency caused by linkage disequilibrium (LD) and sample overlap between different studies. To assess the performance of different methods in the presence of these two challenges, we first conducted comprehensive simulations with diverse LD patterns and sample overlaps. Then we applied these methods to real GWAS summary statistics for a wide spectrum of complex traits. Based on these experiments, we conclude that methods relying on accurate LD estimation are less robust in real data applications due to the imprecision of LD obtained from reference panels. Our findings offer guidance on how to choose appropriate methods for genetic correlation estimation in post-GWAS analysis.
['Zhang|Yiliang|Y|0000-0002-9851-7870', 'Cheng|Youshu|Y|', 'Jiang|Wei|W|0000-0001-6120-5278', 'Ye|Yixuan|Y|', 'Lu|Qiongshi|Q|0000-0002-4514-0969', 'Zhao|Hongyu|H|']
D019985:Benchmarking D015331:Cohort Studies D003198:Computer Simulation D000068598:Data Accuracy D005787:Gene Frequency D015894:Genome, Human D055106:Genome-Wide Association Study D005838:Genotype D006801:Humans D015810:Linkage Disequilibrium D020412:Multifactorial Inheritance D010641:Phenotype D020641:Polymorphism, Single Nucleotide
genetic correlation complex traits GWAS summary statistics benchmarking