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Genetics and Epigenetics

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



Admixed populations are a resource to study the global genetic architecture of complex phenotypes, which is critical, considering that non-European populations are severely underrepresented in genomic studies. Here, we study the genetic architecture of BMI in children, young adults, and elderly individuals from the admixed population of Brazil.


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 Brazilian population-based cohorts from Northeast (Salvador), Southeast (Bambuí), and South (Pelotas).


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 = 2.76e−06). This variant is 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 women with morbid obesity from Pelotas, São Paulo, and Bambuí. The effect size of rs114066381 is at least five times higher than the FTO SNPs rs9939609 and rs1558902, already emblematic for their high effects.


We identified six candidate SNPs associated with BMI. rs114066381 stands out for its high effect that was replicated and its high frequency in women with morbid obesity. We demonstrate how admixed populations are a source of new relevant phenotype-associated genetic variants.

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Fig. 1: Admixture in the Brazilian cohorts, BMI distributions, and admixture mapping (AM) Manhattan plots with significant peaks.
Fig. 2: LocusZoom plot of the fine-mapping of consensus significant admixture mapping peak in young adults from Pelotas at 13q12.3 associated with European ancestry in females performed using both genotyped and imputed SNPs ±1 Mb from target region (lead windows).
Fig. 3: Body mass index (BMI) in females and males’ adults from Pelotas cohort, according to their genotypes in the SNP rs114066381.
Fig. 4: Forest plots from the meta-analysis synthesizing association results between rs114066381 and BMI from seven populations.

Code availability

Used bioinformatics pipelines are available in the EPIGEN-Brazil Project Scientific Workflow (, [34]).


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For analyses, we used the Sagarana cluster (from Centro de Laboratórios Multiusuários do Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais). We thank Miguel Ortega for help in the use of Sagarana, Ms. Evelyn Tay at University of Ghana Medical School (Accra, Ghana) for managing the study, and Ms. Marcelle Bartholomeu and Ms. Àlex Teixeira for technical 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), the Minas Gerais State Agency for Support of Research (FAPEMIG), Rede Mineira de Genômica Populacional e Medicina de Precisão (FAPEMIG-RED-00314-16), and TWAS-CNPq Full PhD fellow, and grant 2019/19998-8, São Paulo Research Foundation (FAPESP).

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Correspondence to Eduardo Tarazona-Santos.

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Scliar, M.O., Sant’Anna, H.P., Santolalla, M.L. 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. Int J Obes 45, 1017–1029 (2021).

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