A harmonized public resource of deeply sequenced diverse human genomes
- Zan Koenig1,2,13,
- Mary T. Yohannes1,2,13,
- Lethukuthula L. Nkambule1,2,
- Xuefang Zhao3,4,5,
- Julia K. Goodrich2,3,
- Heesu Ally Kim1,
- Michael W. Wilson3,
- Grace Tiao3,
- Stephanie P. Hao3,4,5,
- Nareh Sahakian6,
- Katherine R. Chao3,
- Mark A. Walker4,7,
- Yunfei Lyu8,
- gnomAD Project Consortium,
- Heidi L. Rehm3,4,
- Benjamin M. Neale1,2,3,9,
- Michael E. Talkowski1,3,4,5,
- Mark J. Daly1,2,3,10,11,
- Harrison Brand3,4,5,
- Konrad J. Karczewski1,2,3,4,9,
- Elizabeth G. Atkinson1,2,12 and
- Alicia R. Martin1,2,3,4
- 1Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA;
- 2Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA;
- 3Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA;
- 4Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA;
- 5Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA;
- 6Broad Genomics, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, 02141, USA;
- 7Data Sciences Platform, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA;
- 8Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA;
- 9Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA;
- 10Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 11Institute for Molecular Medicine Finland, 00290 Helsinki, Finland;
- 12Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
-
↵13 These authors contributed equally to this work.
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.
Footnotes
-
[Supplemental material is available for this article.]
-
Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.278378.123.
- Received August 10, 2023.
- Accepted May 7, 2024.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see https://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.