Significance

The EPIGEN Brazil Project is the largest Latin-American initiative to study the genomic diversity of admixed populations and its effect on phenotypes. We studied 6,487 Brazilians from three population-based cohorts with different geographic and demographic backgrounds. We identified ancestry components of these populations at a previously unmatched geographic resolution. We broadened our understanding of the African diaspora, the principal destination of which was Brazil, by revealing an African ancestry component that likely derives from the slave trade from Bantu/eastern African populations. In the context of the current debate about how the pattern of deleterious mutations varies between Africans and Europeans, we use whole-genome data to show that continental admixture is the main and complex determinant of the amount of deleterious genotypes in admixed individuals.

Abstract

While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genome-wide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil. We showed that ancestry-positive assortative mating permeated Brazilian history. We traced European ancestry in the Southeast/South to a wider European/Middle Eastern region with respect to the Northeast, where ancestry seems restricted to Iberia. By developing an approximate Bayesian computation framework, we infer more recent European immigration to the Southeast/South than to the Northeast. Also, the observed low Native-American ancestry (6–8%) was mostly introduced in different regions of Brazil soon after the European Conquest. We broadened our understanding of the African diaspora, the major destination of which was Brazil, by revealing that Brazilians display two within-Africa ancestry components: one associated with non-Bantu/western Africans (more evident in the Northeast and African Americans) and one associated with Bantu/eastern Africans (more present in the Southeast/South). Furthermore, the whole-genome analysis of 30 individuals (42-fold deep coverage) shows that continental admixture rather than local post-Columbian history is the main and complex determinant of the individual amount of deleterious genotypes.

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Data Availability

Data deposition: The data reported in this paper have been deposited in the European Nucleotide Archive (PRJEB9080 (ERP010139) Genomic Epidemiology of Complex Diseases in Population-Based Brazilian Cohorts), accession no. EGAS00001001245, under EPIGEN Committee Controlled Access mode.

Acknowledgments

The authors thank David Alexander and Fernando Levi Soares for technical help and discussion and Rasmus Nielsen and Mason Liang for sharing their software for continuous specific ancestry simulations and feedback on its use. Centro Nacional de Processamento de Alto Desempenho em MG/Financiadora de Estudos e Projetos–Ministério da Ciência, Tecnologia e Inovação, Centro Nacional de Super Computação, and Programa de Desenvolvimento Tecnológico em Insumos para Saúde-Bioinformatics Platform at Fundação Oswaldo Cruz-Minas Gerais provided computational support. The EPIGEN Brazil Initiative is funded by the Brazilian Ministry of Health (Department of Science and Technology from the Secretaria de Ciência, Tecnologia e Insumos Estratégicos) through Financiadora de Estudos e Projetos. The EPIGEN Brazil investigators received funding from the Brazilian Ministry of Education (CAPES Agency), Brazilian National Research Council (CNPq), Pró-Reitoria de Pesquisa from the Universidade Federal de Minas Gerais, and the Minas Gerais State Agency for Support of Research (FAPEMIG).

Supporting Information

Appendix (PDF)
Supporting Information

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Information & Authors

Information

Published in

Go to Proceedings of the National Academy of Sciences
Go to Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
Vol. 112 | No. 28
July 14, 2015
PubMed: 26124090

Classifications

Data Availability

Data deposition: The data reported in this paper have been deposited in the European Nucleotide Archive (PRJEB9080 (ERP010139) Genomic Epidemiology of Complex Diseases in Population-Based Brazilian Cohorts), accession no. EGAS00001001245, under EPIGEN Committee Controlled Access mode.

Submission history

Published online: June 29, 2015
Published in issue: July 14, 2015

Keywords

  1. Latin America
  2. population genetics
  3. Salvador SCAALA
  4. Bambuí Cohort Study of Ageing
  5. Pelotas Birth Cohort Study

Acknowledgments

The authors thank David Alexander and Fernando Levi Soares for technical help and discussion and Rasmus Nielsen and Mason Liang for sharing their software for continuous specific ancestry simulations and feedback on its use. Centro Nacional de Processamento de Alto Desempenho em MG/Financiadora de Estudos e Projetos–Ministério da Ciência, Tecnologia e Inovação, Centro Nacional de Super Computação, and Programa de Desenvolvimento Tecnológico em Insumos para Saúde-Bioinformatics Platform at Fundação Oswaldo Cruz-Minas Gerais provided computational support. The EPIGEN Brazil Initiative is funded by the Brazilian Ministry of Health (Department of Science and Technology from the Secretaria de Ciência, Tecnologia e Insumos Estratégicos) through Financiadora de Estudos e Projetos. The EPIGEN Brazil investigators received funding from the Brazilian Ministry of Education (CAPES Agency), Brazilian National Research Council (CNPq), Pró-Reitoria de Pesquisa from the Universidade Federal de Minas Gerais, and the Minas Gerais State Agency for Support of Research (FAPEMIG).

Notes

This article is a PNAS Direct Submission.
4A complete list of the Brazilian EPIGEN Project Consortium can be found in SI Appendix.

Authors

Affiliations

Fernanda S. G. Kehdy1
Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil;
Mateus H. Gouveia1
Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil;
Moara Machado1
Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil;
Wagner C. S. Magalhães1
Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil;
Andrea R. Horimoto
Instituto do Coração, Universidade de São Paulo, 05403-900, São Paulo, Sao Paulo, Brazil;
Bernardo L. Horta
Programa de Pós-Graduação em Epidemiologia, Universidade Federal de Pelotas, 464, 96001-970 Pelotas, Rio Grande do Sul, Brazil;
Rennan G. Moreira
Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil;
Thiago P. Leal
Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil;
Marilia O. Scliar
Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil;
Giordano B. Soares-Souza
Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil;
Fernanda Rodrigues-Soares
Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil;
Gilderlanio S. Araújo
Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil;
Roxana Zamudio
Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil;
Hanaisa P. Sant Anna
Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil;
Hadassa C. Santos
Instituto do Coração, Universidade de São Paulo, 05403-900, São Paulo, Sao Paulo, Brazil;
Nubia E. Duarte
Instituto do Coração, Universidade de São Paulo, 05403-900, São Paulo, Sao Paulo, Brazil;
Rosemeire L. Fiaccone
Departamento de Estatística, Instituto de Matemática, Universidade Federal da Bahia, 40170-110, Salvador, Bahia, Brazil;
Camila A. Figueiredo
Departamento de Ciências da Biointeração, Instituto de Ciências da Saúde, Universidade Federal da Bahia, 40110-100, Salvador, Bahia, Brazil;
Thiago M. Silva
Instituto de Saúde Coletiva, Universidade Federal da Bahia, 40110-040, Salvador, Bahia, Brazil;
Gustavo N. O. Costa
Instituto de Saúde Coletiva, Universidade Federal da Bahia, 40110-040, Salvador, Bahia, Brazil;
Sandra Beleza
Department of Genetics, University of Leicester, LE1 7RH, Leicester, United Kingdom;
Douglas E. Berg
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110;
Department of Medicine, University of California, San Diego, CA 92093;
Lilia Cabrera
Biomedical Research Unit, Asociación Benéfica Proyectos en Informática, Salud, Medicina y Agricultura (AB PRISMA), 170070, Lima, Peru;
Guilherme Debortoli
Departamento de Biologia Celular, Embriologia e Genética, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, Santa Catarina, Brazil;
Denise Duarte
Departamento de Estatística, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil;
Silvia Ghirotto
Dipartimento di Scienze della Vita e Biotecnologie, Università di Ferrara, 44121 Ferrara, Italy;
Robert H. Gilman
Bloomberg School of Public Health, International Health, Johns Hopkins University, Baltimore, MD 21205;
Laboratorio de Investigación de Enfermedades Infecciosas, Universidade Peruana Cayetano Heredia, 15102, Lima, Peru;
Vanessa F. Gonçalves
Department of Psychiatry and Neuroscience Section, Center for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada M5T 1R8;
Andrea R. Marrero
Departamento de Biologia Celular, Embriologia e Genética, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, Santa Catarina, Brazil;
Yara C. Muniz
Departamento de Biologia Celular, Embriologia e Genética, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, Santa Catarina, Brazil;
Hansi Weissensteiner
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, 6020 Innsbruck, Austria;
Meredith Yeager
Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 20850;
Laura C. Rodrigues
Department of Infectious Disease Epidemiology, Faculty of Epidemiology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom;
Mauricio L. Barreto
Instituto de Saúde Coletiva, Universidade Federal da Bahia, 40110-040, Salvador, Bahia, Brazil;
M. Fernanda Lima-Costa2
Instituto de Pesquisa Rene Rachou, Fundação Oswaldo Cruz, 30190-002, Belo Horizonte, Minas Gerais, Brazil
Alexandre C. Pereira2
Instituto do Coração, Universidade de São Paulo, 05403-900, São Paulo, Sao Paulo, Brazil;
Maíra R. Rodrigues2
Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil;
Eduardo Tarazona-Santos3,2 [email protected]
Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Minas Gerais, Brazil;
The Brazilian EPIGEN Project Consortium

Notes

3
To whom correspondence should be addressed. Email: [email protected].
Author contributions: E.T.-S. designed research; F.S.G.K., M.H.G., M.M., W.C.S.M., A.R.H., B.L.H., R.G.M., M.L.B., M.F.L.-C., A.C.P., M.R.R., and E.T.-S. performed research; T.P.L., R.Z., R.L.F., C.A.F., T.M.S., G.N.O.C., S.B., D.E.B., L.C., R.H.G., M.Y., L.C.R., M.R.R., and T.B.E.P.C. contributed new reagents/analytic tools; F.S.G.K., M.H.G., M.M., W.C.S.M., A.R.H., R.G.M., T.P.L., M.O.S., G.B.S.-S., F.R.-S., G.S.A., H.P.S.A., H.C.S., N.E.D., G.D., D.D., S.G., V.F.G., A.R.M., Y.C.M., and H.W. analyzed data; F.S.G.K., M.H.G., M.M., W.C.S.M., R.G.M., M.R.R., and E.T.-S. wrote the paper; F.S.G.K. coordinated the ancestry team of the project; W.C.S.M. coordinated the inputation team of the project; A.R.H. coordinated the basic analyses team of the project; B.L.H. coordinated the 1982 Pelotas Birth Cohort; M.L.B. coordinated the SCAALA (Social Changes, Asthma and Allergy in Latin America Program) cohort; M.F.L.-C. coordinated the Bambui cohort; A.C.P. and E.T.-S. supervised the genome analysis group of the project; and M.R.R. coordinated the bioinformatics team of the project.
1
F.S.G.K., M.H.G., M.M., and W.C.S.M. contributed equally to this work.
2
M.F.L.-C., A.C.P., M.R.R., and E.T.-S. contributed equally to this work.

Competing Interests

The authors declare no conflict of interest.

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    Origin and dynamics of admixture in Brazilians and its effect on the pattern of deleterious mutations
    Proceedings of the National Academy of Sciences
    • Vol. 112
    • No. 28
    • pp. 8511-E3752

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