1 Ontario Institute for Cancer Research; Toronto, Ontario, Canada.
2 Department of Molecular Genetics, University of Toronto; Toronto, Ontario, Canada.
3 Vector Institute; Toronto, Ontario, Canada.
4 Department of Mathematics, Wilfrid Laurier University; Waterloo, Ontario, Canada.
5 Division of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand; Johannesburg, South Africa.
6 Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of Witwatersrand; Johannesburg, South Africa.
7 Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center; New York, United States.
8 College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University; Kampala, Uganda.
9 School of Biological Sciences, University of Liverpool; Liverpool United Kingdom.
10 School of Biodiversity, One Health & Veterinary Medicine, University of Glasgow; Glasgow, United Kingdom.
11 School of Electrical and Information Engineering, University of Witwatersrand; Johannesburg, South Africa.
12 Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand; Johannesburg, South Africa.
13 Department of Biology, Concordia University; Montreal, Quebec, Canada.
14 Nuffield Department of Population Health, Big Data Institute, University of Oxford; Oxford, United Kingdom.

Clonal hematopoiesis, through the age-associated accumulation of somatic mutations in blood, is strongly associated with hematological malignancies and other chronic diseases. These mutations have largely been characterized in individuals of European ancestry or environments, and consequently, it remains unclear how mutation-recurrence patterns vary across populations of different histories or non-European ancestries. Here, we evaluate how variation in geography, ancestry, genetics and sex shape the prevalence of mosaic chromosomal alterations (mCAs) among 47,369 individuals from the Canadian Partnership for Tomorrow's Health, including a founding population cohort in Quebec, and 13,562 individuals from within South, Central, West and East Africa though the H3Africa consortium. We identified autosomal mCA hotspots that were ancestry- and sex-specific, mapped novel ancestry-specific germline variants associated with autosomal mCA prevalence, and estimated heritability rates to quantify the germline genetic contribution to autosomal mCA variance. We also showed how mCAs impact blood transcriptomes, implicating stabilizing selection as a mechanism by which copy number gain mutations are tolerated in healthy blood. Collectively, mapping the landscape of autosomal mCAs in populations of diverse ancestry illustrates similarities but also highlights important ancestry, geographic, and sex-specific differences.