A harmonized public resource of deeply sequenced diverse human genomes.
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, gnomAD Project Consortium, Heidi L Rehm, Benjamin M Neale, Michael E Talkowski, Mark J Daly, Harrison Brand, Konrad J Karczewski, Elizabeth G Atkinson, Alicia R Martin
Author Information
Zan Koenig: Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Mary T Yohannes: Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Lethukuthula L Nkambule: Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Xuefang Zhao: Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Julia K Goodrich: Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Heesu Ally Kim: Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Michael W Wilson: Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Grace Tiao: Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Stephanie P Hao: Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Nareh Sahakian: Broad Genomics, The Broad Institute of MIT and Harvard, 320 Charles Street, Cambridge, MA, 02141, USA.
Katherine R Chao: Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Mark A Walker: Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Yunfei Lyu: Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Heidi L Rehm: Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ORCID
Benjamin M Neale: Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ORCID
Michael E Talkowski: Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Mark J Daly: Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ORCID
Harrison Brand: Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Konrad J Karczewski: Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Elizabeth G Atkinson: Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ORCID
Alicia R Martin: Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ORCID
Underrepresented populations are often excluded from genomic studies due 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 4,094 whole genomes from 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 demonstrate substantial added value from this dataset compared to 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 to 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.
References
Am J Hum Genet. 2013 Aug 8;93(2):278-88
[PMID: 23910464]
