Genome-wide LD scores enable robust heritability and genetic correlation estimation from summary statistics across genetic ancestries
- 1University of California, Los Angeles
Abstract
Our knowledge of human complex trait architecture across diverse populations remains limited. Estimating SNP heritability and genetic correlation from GWAS summary statistics - successful in revealing genetic architecture in homogeneous cohorts - is challenging in structured and admixed populations due, in part, to the difficulty of representing long-range LD. We present SUMMIT, a statistical framework that combines genome-wide LD scores, efficiently estimated using random projections, with GWAS summary statistics to estimate genome-wide and annotation-specific heritability and genetic correlation. In simulations that explore diverse aspects of genetic architecture across European (EUR), South Asian (SAS), and admixed African-European cohorts (AFR) in the UK Biobank (UKB), SUMMIT had increased accuracy and reduced bias compared to prior methods, with the largest gains in non-European ancestries reflecting improved modeling of long-range LD. Across 40 UKB traits, SUMMIT produced estimates of genome-wide common-SNP heritability (h_g^2) and heritability enrichments in genomic annotations that were broadly concordant across ancestries with the SUMMIT h_g^2 estimates more closely matching recent whole-genome sequencing based estimates. SUMMIT substantially improved genetic correlation analysis recovering more significant findings across ancestries (23 SAS and 3 AFR at FDR < 0.05 compared with none and two for cov-LDSC) with the non-European discoveries showing concordant effects in Europeans suggesting that, like heritability, global patterns of pleiotropy are largely shared across ancestries. By combining accurate genome-wide LD and efficient moment estimation, SUMMIT enables investigation into how heritability and genetic correlation vary across populations and genomic annotations, including in structured and admixed cohorts, at the genome-wide, annotation-specific, and cross-trait levels.
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BibTeX
@misc{jeong2026genomewide,
title = {{Genome-wide LD scores enable robust heritability and genetic correlation estimation from summary statistics across genetic ancestries}},
author = {M. Jeong and Z. Liu and J. Ni and U. An and S. Han and A. Anand and P. Anand and M. Boffelli and S. Sankararaman},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.20.760508},
url = {https://www.biorxiv.org/content/10.64898/2026.10.20.760508v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Genome-wide LD scores enable robust heritability and genetic correlation estimation from summary statistics across genetic ancestries
AU - M. Jeong
AU - Z. Liu
AU - J. Ni
AU - U. An
AU - S. Han
AU - A. Anand
AU - P. Anand
AU - M. Boffelli
AU - S. Sankararaman
PY - 2026
DA - 2026/10/20
PB - bioRxiv
DO - 10.64898/2026.10.20.760508
UR - https://www.biorxiv.org/content/10.64898/2026.10.20.760508v1
AB - Our knowledge of human complex trait architecture across diverse populations remains limited. Estimating SNP heritability and genetic correlation from GWAS summary statistics - successful in revealing genetic architecture in homogeneous cohorts - is challenging in structured and admixed populations due, in part, to the difficulty of representing long-range LD. We present SUMMIT, a statistical framework that combines genome-wide LD scores, efficiently estimated using random projections, with GWAS summary statistics to estimate genome-wide and annotation-specific heritability and genetic correlation. In simulations that explore diverse aspects of genetic architecture across European (EUR), South Asian (SAS), and admixed African-European cohorts (AFR) in the UK Biobank (UKB), SUMMIT had increased accuracy and reduced bias compared to prior methods, with the largest gains in non-European ancestries reflecting improved modeling of long-range LD. Across 40 UKB traits, SUMMIT produced estimates of genome-wide common-SNP heritability (h_g^2) and heritability enrichments in genomic annotations that were broadly concordant across ancestries with the SUMMIT h_g^2 estimates more closely matching recent whole-genome sequencing based estimates. SUMMIT substantially improved genetic correlation analysis recovering more significant findings across ancestries (23 SAS and 3 AFR at FDR < 0.05 compared with none and two for cov-LDSC) with the non-European discoveries showing concordant effects in Europeans suggesting that, like heritability, global patterns of pleiotropy are largely shared across ancestries. By combining accurate genome-wide LD and efficient moment estimation, SUMMIT enables investigation into how heritability and genetic correlation vary across populations and genomic annotations, including in structured and admixed cohorts, at the genome-wide, annotation-specific, and cross-trait levels.
ER -