Last updated:
Author(s):
Hui Li, Rahul Mazumder, Xihong Lin
Publish date:
2 December 2023
Journal:
Nature Communications
PubMed ID:
38040712

Abstract

Existing SNP-heritability estimators that leverage summary statistics from genome-wide association studies (GWAS) are much less efficient (i.e., have larger standard errors) than the restricted maximum likelihood (REML) estimators which require access to individual-level data. We introduce a new method for local heritability estimation – Heritability Estimation with high Efficiency using LD and association Summary Statistics (HEELS) – that significantly improves the statistical efficiency of summary-statistics-based heritability estimator and attains comparable statistical efficiency as REML (with a relative statistical efficiency >92%). Moreover, we propose representing the empirical LD matrix as the sum of a low-rank matrix and a banded matrix. We show that this way of modeling the LD can not only reduce the storage and memory cost, but also improve the computational efficiency of heritability estimation. We demonstrate the statistical efficiency of HEELS and the advantages of our proposed LD approximation strategies both in simulations and through empirical analyses of the UK Biobank data.

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We aim to develop and apply a suite of scalable, powerful, and robust tools that can further identify the genomic determinants of health and disease,…

Institution:
Harvard School of Public Health, United States of America

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