Genomic ancestry and ethnoracial self-classification based on 5,871 community-dwelling Brazilians (The Epigen Initiative)

Lima‐Costa, Maria Fernanda; Rodrigues, LC; Ml, Barreto; Gouveia, Mateus H.; Bl, Horta; Mambrini, Juliana Vaz de Melo; Kehdy, Fernanda S. G.; Pereira, Alexandre C.; Rodrigues‐Soares, Fernanda; Victora, Cesar G; Tarazona‐Santos, Eduardo

doi:10.1038/srep09812

Cited by 129 publications

(172 citation statements)

References 27 publications

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“…Continental genomic ancestry in Latin America (and specifically, in Brazil) is correlated with a set of phenotypes, such as skin color and self-reported ethnicity, and social and cultural features, such as socioeconomic status (15)(16)(17). We observed a positive correlation across the three EPIGEN populations between SNP-specific Africans/Europeans F ST (a measurement of informativeness of ancestry) and SNP-specific F IT (a measurement of departure from Hardy-Weinberg equilibrium) …”

Section: Resultsmentioning

confidence: 99%

Origin and dynamics of admixture in Brazilians and its effect on the pattern of deleterious mutations

Kehdy

Gouveia

Machado

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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225

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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 genomewide 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.Latin America | population genetics | Salvador SCAALA | Bambuí Cohort Study of Ageing | Pelotas Birth Cohort Study L atin Americans, who are classical models of the effects of admixture in human populations (1, 2), remain underrepresented in studies of human genomic diversity, notwithstanding recent studies (3, 4). Indeed, no large genome-wide study on admixed South Americans has been conducted so far. Brazil is the largest and most populous Latin-American country. Its over 200 million inhabitants are the product of post-Columbian admixture between Amerindians, Europeans colonizers or immigrants, and African slaves (1). Interestingly, Brazil was the destiny of nearly 40% of the African diaspora, receiving seven times more slaves than the United States (nearly 4 million vs. 600,000).Here, we present results of the EPIGEN Brazil Initiative (https:// epigen.grude.ufmg.br), the most comprehensive up-to-date genomic analysis of a Latin-American population. We genotyped nearly 2.2 million SNPs in 6,487 admixed individuals from three population-based cohorts from different regions with distinct demographic and socioeconomic backgrounds and sequenced the whole genome of 30 individuals from these populations at an To whom correspondence should be addressed. Email: edutars@ic...

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Section: Resultsmentioning

confidence: 99%

Origin and dynamics of admixture in Brazilians and its effect on the pattern of deleterious mutations

Kehdy

Gouveia

Machado

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…In SCAALA (the discovery sample) rs12007907 MAF (corresponding to the A allele) was 25%, reflecting the remarkable African contribution to this admixed population. 45 In the ProAr cohort the frequency of this SNP was 23%, which reflects the closest genetic similarity of this population with the discovery sample. However, in the GALA II and Pelotas cohorts the MAFs were 7 and 11%, respectively, which may result in a lack of statistical power to detect an association.…”

Section: Discussionmentioning

confidence: 75%

“…Furthermore, the function of IL1RAPL might be more related to the Toll-like receptors subfamily than IL1R subfamily. 45 Interestingly, IL1RAPL1 has already been reported in two previous GWAS to be associated with cardiovascular disease 47 and autism. 19 Although this gene belongs to the IL1R family, it has been poorly studied, possible due to its localization in the X chromosome and consequent exclusion from genome-wide analysis.…”

Section: Discussionmentioning

confidence: 93%

“…The expression of IL1RAPL protein has been detected in the brain, heart and muscle. 45 Khan et al showed that IL1RAPL can active c-Jun amino-terminal kinases (JNKs) but not extracellular signal-regulated kinases (ERKs) nor mitogen-activated protein kinases (MAPKs). 46 Although IL1R have high affinities for their ligands, the accessory proteins cannot do it directly.…”

Section: Discussionmentioning

confidence: 99%

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Suggestive association between variants in IL1RAPL and asthma symptoms in Latin American children

et al. 2017

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Several genome-wide association studies have been conducted to investigate the influence of genetic polymorphisms in the development of allergic diseases, but few of them have included the X chromosome. The aim of present study was to perform an X chromosome-wide association study (X-WAS) for asthma symptoms. The study included 1307 children of which 294 were asthma cases. DNA was genotyped using 2.5 HumanOmni Beadchip from Illumina. Statistical analyses were performed in PLINK 1.9, MACH 1.0 and Minimac2. The variant rs12007907 (g.29483892C4A) in IL1RAPL gene was suggestively associated with asthma symptoms in discovery set (odds ratio (OR) = 0.49, 95% confidence interval (CI): 0.37-0.67; P = 3.33 × 10 −6 ). This result was replicated in the ProAr cohort in men only (OR = 0.45, 95% CI: 0.21-0.95; P = 0.038). Furthermore, investigating the functional role of the rs12007907 on the production a Th2-type cytokine, IL-13, we found a negative association between the minor allele A with IL-13 production in the discovery set (P = 0.044). Gene-based analysis revealed that NUDT10 was the most consistently associated with asthma symptoms in discovery sample. In conclusion, the rs12007907 variant in IL1RAPL gene was negatively associated with asthma and IL-13 production in our study and a sex-specific association was observed in one of the validation samples. It suggests an effect on asthma susceptibility and may explain differences in severe asthma frequency between women and men.

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“…The study also demonstrated that European ancestry is predominant in Pelotas (85.3%). 39 In our analyses, we dichotomized the variable skin colour as white (66.8%) and others (33.2%).…”

Section: Resultsmentioning

confidence: 99%

COMT and DAT1 genes are associated with hyperactivity and inattention traits in the 1993 Pelotas Birth Cohort: evidence of sex-specific combined effect

Akutagava-Martins

Salatino-Oliveira

Kieling

et al. 2016

jpn

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IntroductionSymptoms of hyperactivity/impulsivity and inattention are dimensionally distributed in the population. Evidence supporting this idea comes from the study of twin pairs from the general population, which demonstrate high heritability estimates for these behavioural traits, ranging from 0.60 to 0.91. [1][2][3] The low end of the distribution would be represented by few behavioural problems and better cognitive function than the high and symptomatic end. This extreme and impairing end would probably be represented by the categorical diagnosis of attention-deficit/hyperactivity disorder (ADHD).4 A study on inhibition, an executive function whose impairments are part of the cognitive deficits seen in individuals with ADHD, demonstrated that performance on inhibition-related tasks were positively associated with ADHD-like traits in a large sample of healthy adults who did not have a first-degree relative with ADHD. 5The heritability estimates for ADHD are essentially the same for both continuous and categorical approaches, consistent with a dimensional view of ADHD and a strong genetic component. [1][2][3]6 Based on the normal distribution of ADHD traits in the general population, the identification and understanding of ADHD susceptibility genes may bene fit from studies of this dimensional characteristic of ADHD in nonclinical samples.2 Despite high heritability estimates, the identification of ADHD genetic susceptibility markers has been difficult, with few replicable findings described so far. 7,8 The main candidates for ADHD molecular genetic studies have been genes involved in the dopamine pathway, given considerable evidence supporting the dopaminergic hypothesis. According to this theory, an Background: Attention-deficit/hyperactivity disorder (ADHD) symptoms are dimensionally distributed in the population. This study aimed to assess the role of the catechol-O-methyltransferase (COMT) and of the dopamine transporter (DAT1) genes on ADHD symptoms in the general population. Methods: We investigated 4101 individuals from the 1993 Pelotas Birth Cohort Study using the parent version of the Strengths and Difficulties Questionnaire (SDQ) at ages 11 and 15 years. The SDQ hyperactivity/inattention scores were the main outcomes. Results: Linear regression analyses demonstrated that the increasing number of COMT 158 Val and DAT1 10R alleles significantly predicted increasing SDQ hyperactivity/inattention scores in boys at both 11 and 15 years of age (β coefficient = 0.049, t = 2.189, p = 0.029, R 2 = 0.012, and β coefficient = 0.064, t = 2.832, p = 0.005, R 2 = 0.008, respectively). The presence of both COMT 158 Val and DAT1 10R alleles was also associated with full categorical ADHD diagnosis at 18 years of age in boys (χ 2 = 4.561, p = 0.033, odds ratio 2.473, 95% confidence interval 1.048-5.838) from this cohort. We did not observe these associations in girls. Limitations: Our analyses of SDQ hyperactivity/inattention scores were not corrected for SDQ scores of conduct problems because these variables were h...

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Genomic ancestry and ethnoracial self-classification based on 5,871 community-dwelling Brazilians (The Epigen Initiative)

Cited by 129 publications

References 27 publications

Origin and dynamics of admixture in Brazilians and its effect on the pattern of deleterious mutations

Origin and dynamics of admixture in Brazilians and its effect on the pattern of deleterious mutations

Suggestive association between variants in IL1RAPL and asthma symptoms in Latin American children

COMT and DAT1 genes are associated with hyperactivity and inattention traits in the 1993 Pelotas Birth Cohort: evidence of sex-specific combined effect

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