High-definition likelihood inference of genetic correlations across human complex traits
Open Access
- 29 June 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 52 (8), 859-864
- https://doi.org/10.1038/s41588-020-0653-y
Abstract
Genetic correlation is a central parameter for understanding shared genetic architecture between complex traits. By using summary statistics from genome-wide association studies (GWAS), linkage disequilibrium score regression (LDSC) was developed for unbiased estimation of genetic correlations. Although easy to use, LDSC only partially utilizes LD information. By fully accounting for LD across the genome, we develop a high-definition likelihood (HDL) method to improve precision in genetic correlation estimation. Compared to LDSC, HDL reduces the variance of genetic correlation estimates by about 60%, equivalent to a 2.5-fold increase in sample size. We apply HDL and LDSC to estimate 435 genetic correlations among 30 behavioral and disease-related phenotypes measured in the UK Biobank (UKBB). In addition to 154 significant genetic correlations observed for both methods, HDL identified another 57 significant genetic correlations, compared to only another 2 significant genetic correlations identified by LDSC. HDL brings more power to genomic analyses and better reveals the underlying connections across human complex traits.Funding Information
- Vetenskapsrådet (2017-02543)
This publication has 16 references indexed in Scilit:
- SumHer better estimates the SNP heritability of complex traits from summary statisticsNature Genetics, 2018
- The UK Biobank resource with deep phenotyping and genomic dataNature, 2018
- Estimation of Genetic Correlation via Linkage Disequilibrium Score Regression and Genomic Restricted Maximum LikelihoodAmerican Journal of Human Genetics, 2018
- LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysisBioinformatics, 2016
- Contrasting genetic architectures of schizophrenia and other complex diseases using fast variance-components analysisNature Genetics, 2015
- Genome-wide genetic homogeneity between sexes and populations for human height and body mass indexHuman Molecular Genetics, 2015
- An atlas of genetic correlations across human diseases and traitsNature Genetics, 2015
- LD Score regression distinguishes confounding from polygenicity in genome-wide association studiesNature Genetics, 2015
- Estimation of pleiotropy between complex diseases using single-nucleotide polymorphism-derived genomic relationships and restricted maximum likelihoodBioinformatics, 2012
- Common SNPs explain a large proportion of the heritability for human heightNature Genetics, 2010