Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass- and fat mass- indexes
| Autor(a) principal: | |
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| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/48002 |
Resumo: | Mauricio Lima Barreto - Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Centro de Integração de Dados e Conhecimento para Saúde. Salvador, BA, Brasil. Sérgio Viana Peixoto, Mateus H Gouveia - Fundação Oswaldo Cruz. Instituto de Pesquisas René Rachou. Belo Horizonte, MG, Brasil. Fernanda SG Kehdy - Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. |
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Scliar, Marilia O.Sant Anna, Hanaisa P.Santolalla, Meddly L.Leal, Thiago P.Araújo, Nathalia M.Alvim, IsabelaBorda, VictorMagalhães, Wagner C. S.Gouveia, Mateus H.Lyra, RicardoMachado, MoaraMichelin, LucasRodrigues, Maíra R.Araújo, Gilderlanio S.Kehdy, Fernanda S. G.Zolini, CamilaPeixoto, Sérgio VianaLuizon, MarceloLobo, FranciscoNaslavsky, Michel S.Yamamoto, Guilherme L.Duarte, Yeda A. O.Hansen, Matthew E. B.Norris, Shane A.Gilman, Robert H.Guio, HeinnerHsing, Ann W.Mbulaiteye, Sam M.Mensah, JamesDutil, JulieYeager, MeredithYeboah, EdwardTishkoff, Sarah A.Choudhury, AnanyoRamsay, MicheleBueno, Maria Rita PassosZatz, MayanaO´Connor, Timothy D.Pereira, Alexandre C.Barreto, Mauricio LimaCosta, Maria Fernanda LimaHorta, Bernardo L.Santos, Eduardo Tarazona2021-07-06T11:34:56Z2021-07-06T11:34:56Z2021SCLIAR, Marilia O. et al. Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass- and fat mass- indexes. International Journal of Obesity, p. 1-29, 2021.0307-0565https://www.arca.fiocruz.br/handle/icict/4800210.1101/827311Mauricio Lima Barreto - Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Centro de Integração de Dados e Conhecimento para Saúde. Salvador, BA, Brasil. Sérgio Viana Peixoto, Mateus H Gouveia - Fundação Oswaldo Cruz. Instituto de Pesquisas René Rachou. Belo Horizonte, MG, Brasil. Fernanda SG Kehdy - Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.1 Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. 2 Human Genome and Stem Cell Research Center, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, Brazil. 3 Melbourne Integrative Genomics, The University of Melbourne, Melbourne, VIC 3052, Australia. 4 Emerge, Emerging Diseases and Climate Change Research Unit, School of Public Health and Administration, Universidad Peruana Cayetano Heredia, Lima, Peru 5 Departamento de Estatística, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil. 6 Instituto de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil. 7 Laboratório de Bioinformática, LABINFO. Laboratório Nacional de Computação Científica (LNCC). Petrópolis, Rio de Janeiro - Brazil 8 Núcleo de Ensino e Pesquisa, Instituto Mário Penna, Belo Horizonte, MG, Brazil. 9 Center for Research on Genomics and Global Health, National Human Genome Research Institute, Bethesda, MD, USA 10 Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, Brazil. 11 Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará - Campus Guamá, Belém, PA, 66075-110, Brazil. 12 Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil. 13 Beagle, Belo Horizonte, MG, 31270-901, Brazil. 14 Mosaico Translational Genomics Initiative, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil. 15 Department of Clinical Genetics, Children's Hospital, Medical School, Universidade de São Paulo, São Paulo, SP, Brazil. 16 Department of Epidemiology, Public Health School, Universidade de São Paulo, São Paulo, SP, Brazil. 17 School of Nursing, Universidade de São Paulo, São Paulo, SP, Brazil. 18 Departments of Biology and Genetics, University of Pennsylvania, Philadelphia, PA, USA. 19 MRC/Wits Developmental Pathways for Health Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 20 Department of International Health, Johns Hopkins School of Public Health, Baltimore, MD, USA. 21 Instituto Nacional de Salud, Lima, Peru. 22 Stanford Cancer Institute, Stanford University, Stanford, CA, USA. 23 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. 24 University of Ghana Medical School, Accra, Ghana. 25 Cancer Biology Division, Ponce Research Institute, Ponce Health Sciences University, Ponce, Puerto Rico 26 Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA. 27 Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 28 Division of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 29 Institute of Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA 30 Program in Personalized and Genomic Medicine, University of Maryland School of Medicine 31 Department of Medicine, University of Maryland School of Medicine 32 Instituto do Coração, Universidade de São Paulo, São Paulo, SP, Brazil. 33 Instituto de Saúde Coletiva, Universidade Federal da Bahia, 40110-040, Salvador, BA, Brazil. 34 Center for Data and Knowledge Integration for Health, Institute Gonçalo Muniz, Fundação Oswaldo Cruz, Salvador, BA, Brazil. 35 Programa de Pós-Graduação em Epidemiologia, Universidade Federal de Pelotas, Pelotas, RS, Brazil. 36 Universidad Peruana Cayetano Heredia, Lima, Peru. 37 Instituto de Estudos Avançados Transdisciplinares, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.Brazilian Ministry of Education (CAPES Agency), Brazilian National Research Council (CNPq), the Minas Gerais State Agency for Support of Research (FAPEMIG) and TWAS-CNPq PhD fellow.Múltipla - Ver em Notas.Admixed populations are a resource to study the global genetic architecture of complex phenotypes, which is critical, considering that non-European populations are severely under-represented in genomic studies. Leveraging admixture in Brazilians, whose chromosomes are mosaics of fragments of Native American, European and African origins, we used genome-wide data to perform admixture mapping/fine-mapping of Body Mass Index (BMI) in three population-based cohorts from Northeast (Salvador), Southeast (Bambuí) and South (Pelotas) of the country. We found significant associations with African-associated alleles in children from Salvador (PALD1 and ZMIZ1 genes), and in young adults from Pelotas (NOD2 and MTUS2 genes). More importantly, in Pelotas, rs114066381, mapped in a potential regulatory region, is significantly associated only in females (p= 2.76 e-06). This variant is very rare in Europeans but with frequencies of ~3% in West Africa, and has a strong female-specific effect (95%CI: 2.32-5.65 kg/m2 per each A allele). We confirmed this sex-specific association and replicated its strong effect for an adjusted fat-mass index in the same Pelotas cohort, and for BMI in another Brazilian cohort from São Paulo (Southeast Brazil). A meta-analysis confirmed the significant association. Remarkably, we observed that while the frequency of rs114066381-A allele ranges from 0.8 to 2.1% in the studied populations, it attains ~9% among morbidly obese women from Pelotas, São Paulo, and Bambuí. The effect size of rs114066381 is at least five-times the effect size of the FTO SNPs rs9939609 and rs1558902, already emblematic for their high effects, and for which we replicated associations in Pelotas. We demonstrate how, after a decade of GWAS mostly performed in European-ancestry populations, non-European and admixed populations are a source of new relevant phenotype-associated genetic variants.engSpringer NatureÍndice de Massa CorporalGenomaPopulaçãoCromossomosPolimorfismo de Nucleotídeo ÚnicoÁfrica OcidentalBody Mass IndexGenomePopulationChromosomesPolymorphism, Single NucleotideAfrica, WesternAdmixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass- and fat mass- indexesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83097https://www.arca.fiocruz.br/bitstream/icict/48002/1/license.txt36b51ef91c52b5338d9d29ba0cc807bcMD51ORIGINALScilar, Marilia O. Admisture... 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| dc.title.pt_BR.fl_str_mv |
Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass- and fat mass- indexes |
| title |
Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass- and fat mass- indexes |
| spellingShingle |
Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass- and fat mass- indexes Scliar, Marilia O. Índice de Massa Corporal Genoma População Cromossomos Polimorfismo de Nucleotídeo Único África Ocidental Body Mass Index Genome Population Chromosomes Polymorphism, Single Nucleotide Africa, Western |
| title_short |
Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass- and fat mass- indexes |
| title_full |
Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass- and fat mass- indexes |
| title_fullStr |
Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass- and fat mass- indexes |
| title_full_unstemmed |
Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass- and fat mass- indexes |
| title_sort |
Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass- and fat mass- indexes |
| author |
Scliar, Marilia O. |
| author_facet |
Scliar, Marilia O. Sant Anna, Hanaisa P. Santolalla, Meddly L. Leal, Thiago P. Araújo, Nathalia M. Alvim, Isabela Borda, Victor Magalhães, Wagner C. S. Gouveia, Mateus H. Lyra, Ricardo Machado, Moara Michelin, Lucas Rodrigues, Maíra R. Araújo, Gilderlanio S. Kehdy, Fernanda S. G. Zolini, Camila Peixoto, Sérgio Viana Luizon, Marcelo Lobo, Francisco Naslavsky, Michel S. Yamamoto, Guilherme L. Duarte, Yeda A. O. Hansen, Matthew E. B. Norris, Shane A. Gilman, Robert H. Guio, Heinner Hsing, Ann W. Mbulaiteye, Sam M. Mensah, James Dutil, Julie Yeager, Meredith Yeboah, Edward Tishkoff, Sarah A. Choudhury, Ananyo Ramsay, Michele Bueno, Maria Rita Passos Zatz, Mayana O´Connor, Timothy D. Pereira, Alexandre C. Barreto, Mauricio Lima Costa, Maria Fernanda Lima Horta, Bernardo L. Santos, Eduardo Tarazona |
| author_role |
author |
| author2 |
Sant Anna, Hanaisa P. Santolalla, Meddly L. Leal, Thiago P. Araújo, Nathalia M. Alvim, Isabela Borda, Victor Magalhães, Wagner C. S. Gouveia, Mateus H. Lyra, Ricardo Machado, Moara Michelin, Lucas Rodrigues, Maíra R. Araújo, Gilderlanio S. Kehdy, Fernanda S. G. Zolini, Camila Peixoto, Sérgio Viana Luizon, Marcelo Lobo, Francisco Naslavsky, Michel S. Yamamoto, Guilherme L. Duarte, Yeda A. O. Hansen, Matthew E. B. Norris, Shane A. Gilman, Robert H. Guio, Heinner Hsing, Ann W. Mbulaiteye, Sam M. Mensah, James Dutil, Julie Yeager, Meredith Yeboah, Edward Tishkoff, Sarah A. Choudhury, Ananyo Ramsay, Michele Bueno, Maria Rita Passos Zatz, Mayana O´Connor, Timothy D. Pereira, Alexandre C. Barreto, Mauricio Lima Costa, Maria Fernanda Lima Horta, Bernardo L. Santos, Eduardo Tarazona |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Scliar, Marilia O. Sant Anna, Hanaisa P. Santolalla, Meddly L. Leal, Thiago P. Araújo, Nathalia M. Alvim, Isabela Borda, Victor Magalhães, Wagner C. S. Gouveia, Mateus H. Lyra, Ricardo Machado, Moara Michelin, Lucas Rodrigues, Maíra R. Araújo, Gilderlanio S. Kehdy, Fernanda S. G. Zolini, Camila Peixoto, Sérgio Viana Luizon, Marcelo Lobo, Francisco Naslavsky, Michel S. Yamamoto, Guilherme L. Duarte, Yeda A. O. Hansen, Matthew E. B. Norris, Shane A. Gilman, Robert H. Guio, Heinner Hsing, Ann W. Mbulaiteye, Sam M. Mensah, James Dutil, Julie Yeager, Meredith Yeboah, Edward Tishkoff, Sarah A. Choudhury, Ananyo Ramsay, Michele Bueno, Maria Rita Passos Zatz, Mayana O´Connor, Timothy D. Pereira, Alexandre C. Barreto, Mauricio Lima Costa, Maria Fernanda Lima Horta, Bernardo L. Santos, Eduardo Tarazona |
| dc.subject.other.pt_BR.fl_str_mv |
Índice de Massa Corporal Genoma População Cromossomos Polimorfismo de Nucleotídeo Único África Ocidental |
| topic |
Índice de Massa Corporal Genoma População Cromossomos Polimorfismo de Nucleotídeo Único África Ocidental Body Mass Index Genome Population Chromosomes Polymorphism, Single Nucleotide Africa, Western |
| dc.subject.en.pt_BR.fl_str_mv |
Body Mass Index Genome Population Chromosomes Polymorphism, Single Nucleotide Africa, Western |
| description |
Mauricio Lima Barreto - Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Centro de Integração de Dados e Conhecimento para Saúde. Salvador, BA, Brasil. Sérgio Viana Peixoto, Mateus H Gouveia - Fundação Oswaldo Cruz. Instituto de Pesquisas René Rachou. Belo Horizonte, MG, Brasil. Fernanda SG Kehdy - Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. |
| publishDate |
2021 |
| dc.date.accessioned.fl_str_mv |
2021-07-06T11:34:56Z |
| dc.date.available.fl_str_mv |
2021-07-06T11:34:56Z |
| dc.date.issued.fl_str_mv |
2021 |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.citation.fl_str_mv |
SCLIAR, Marilia O. et al. Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass- and fat mass- indexes. International Journal of Obesity, p. 1-29, 2021. |
| dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/48002 |
| dc.identifier.issn.none.fl_str_mv |
0307-0565 |
| dc.identifier.doi.none.fl_str_mv |
10.1101/827311 |
| identifier_str_mv |
SCLIAR, Marilia O. et al. Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass- and fat mass- indexes. International Journal of Obesity, p. 1-29, 2021. 0307-0565 10.1101/827311 |
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https://www.arca.fiocruz.br/handle/icict/48002 |
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eng |
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eng |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Springer Nature |
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Springer Nature |
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reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
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FIOCRUZ |
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Repositório Institucional da FIOCRUZ (ARCA) |
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Repositório Institucional da FIOCRUZ (ARCA) |
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Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ) |
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repositorio.arca@fiocruz.br |
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