| Title: | Leveraging LD eigenvalue regression to improve the estimation of SNP heritability and confounding inflation |
| Journal: | American Journal of Human Genetics |
| Published: | 13 Apr 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/35421325/ |
| DOI: | https://doi.org/10.1016/j.ajhg.2022.03.013 |
Publication 7153
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Heritability is a fundamental concept in genetic studies, measuring the genetic contribution to complex traits and bringing insights about disease mechanisms. The advance of high-throughput technologies has provided many resources for heritability estimation. Linkage disequilibrium (LD) score regression (LDSC) estimates both heritability and confounding biases, such as cryptic relatedness and population stratification, among single-nucleotide polymorphisms (SNPs) by using only summary statistics released from genome-wide association studies. However, only partial information in the LD matrix is utilized in LDSC, leading to loss in precision. In this study, we propose LD eigenvalue regression (LDER), an extension of LDSC, by making full use of the LD information. Compared to state-of-the-art heritability estimating methods, LDER provides more accurate estimates of SNP heritability and better distinguishes the inflation caused by polygenicity and confounding effects. We demonstrate the advantages of LDER both theoretically and with extensive simulations. We applied LDER to 814 complex traits from UK Biobank, and LDER identified 363 significantly heritable phenotypes, among which 97 were not identified by LDSC.5 Authors
- Shuang Song
- Wei Jiang
- Yiliang Zhang
- Lin Hou
- Hongyu Zhao
Enabling scientific discoveries that improve human health