A Harmonized Public Resource of Deeply Sequenced Diverse Human Genomes

Authors

Zan Koenig
Mary T Yohannes
Lethukuthula L Nkambule
Xuefang Zhao
Julia K Goodrich
Heesu Ally Kim
Michael W Wilson
Grace Tiao
Stephanie P Hao
Nareh Sahakian
Katherine R Chao
Mark A Walker
Yunfei Lyu
Heidi L Rehm
Benjamin M Neale
Michael E Talkowski
Mark J Daly
Harrison Brand
Konrad J Karczewski
Elizabeth G Atkinson
Alicia R Martin

Publication Date

6-25-2024

Journal

Genome Research

DOI

10.1101/gr.278378.123

PMID

38749656

PMCID

PMC11216312

PubMedCentral® Posted Date

5-1-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Genome, Human, Databases, Genetic, Human Genome Project, High-Throughput Nucleotide Sequencing, Genetic Variation, Genomics

Abstract

Underrepresented populations are often excluded from genomic studies owing in part to a lack of resources supporting their analyses. The 1000 Genomes Project (1kGP) and Human Genome Diversity Project (HGDP), which have recently been sequenced to high coverage, are valuable genomic resources because of the global diversity they capture and their open data sharing policies. Here, we harmonized a high-quality set of 4094 whole genomes from 80 populations in the HGDP and 1kGP with data from the Genome Aggregation Database (gnomAD) and identified over 153 million high-quality SNVs, indels, and SVs. We performed a detailed ancestry analysis of this cohort, characterizing population structure and patterns of admixture across populations, analyzing site frequency spectra, and measuring variant counts at global and subcontinental levels. We also show substantial added value from this data set compared with the prior versions of the component resources, typically combined via liftOver and variant intersection; for example, we catalog millions of new genetic variants, mostly rare, compared with previous releases. In addition to unrestricted individual-level public release, we provide detailed tutorials for conducting many of the most common quality-control steps and analyses with these data in a scalable cloud-computing environment and publicly release this new phased joint callset for use as a haplotype resource in phasing and imputation pipelines. This jointly called reference panel will serve as a key resource to support research of diverse ancestry populations.

Comments

Associated Data