Mosaic chromosomal alterations in blood across ancestries using whole-genome sequencing
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Megabase-scale mosaic chromosomal alterations (mCAs) in blood are prognostic markers for a host of human diseases. Here, to gain a better understanding of mCA rates in genetically diverse populations, we analyzed whole-genome sequencing data from 67,390 individuals from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program. We observed higher sensitivity with whole-genome sequencing data, compared with array-based data, in uncovering mCAs at low mutant cell fractions and found that individuals of European ancestry have the highest rates of autosomal mCAs and the lowest rates of chromosome X mCAs, compared with individuals of African or Hispanic ancestry. Although further studies in diverse populations will be needed to replicate our findings, we report three loci associated with loss of chromosome X, associations between autosomal mCAs and rare variants in DCPS, ADM17, PPP1R16B and TET2 and ancestry-specific variants in ATM and MPL with mCAs in cis.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Nature Genetics |
| Vol/bind | 55 |
| Udgave nummer | 11 |
| Sider (fra-til) | 1912-1919 |
| Antal sider | 8 |
| ISSN | 1061-4036 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
We thank G. Genovese for helpful discussions on implementing the MoChA pipeline with WGS data. Molecular data for the TOPMed program were supported by the National Heart, Lung and Blood Institute. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the US Department of Health and Human Services. For extended acknowledgements, see Supplementary Note .
Funding Information:
We thank G. Genovese for helpful discussions on implementing the MoChA pipeline with WGS data. Molecular data for the TOPMed program were supported by the National Heart, Lung and Blood Institute. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the US Department of Health and Human Services. For extended acknowledgements, see Supplementary Note 4.
Funding Information:
In the past three years, E.K.S. received grant support from Bayer and Northpond Laboratories. B.P. serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. K.B. is a consultant with Galatea Bio, Inc. M.C. received grant support from Bayer, unrelated to the present work. L.M.R. is a consultant for the TOPMed Administrative Coordinating Center (through Westat). A.G.B. is on the scientific advisory board of TenSixteen Bio unrelated to the present work. P.L.A. serves on the board of Geno.Me Inc. The remaining authors declare no competing interests.
Publisher Copyright:
© 2023, The Author(s).
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