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1.
JAMA Netw Open ; 7(9): e2433546, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39283637

RESUMEN

Importance: Racial disparities in prostate cancer are likely the result of complex relationships between both socioeconomic and environmental factors captured by the neighborhood environment and genetic factors, including West African genetic ancestry. However, few studies have examined the combined role of neighborhood environment and genetic ancestry in developing lethal prostate cancer. Objective: To examine the interactions between West African genetic ancestry and neighborhood deprivation in modifying prostate cancer risk and mortality. Design, Setting, and Participants: This case-control study was conducted in the Greater Baltimore area. Participants included men of African and European descent (617 cases with prostate cancer, 852 controls without prostate cancer) enrolled between January 2005 and January 2016. Follow-up was performed through December 31, 2020, using the National Death Index. Analysis was conducted from August 2023 to January 2024. Exposure: Included exposures were West African genetic ancestry, derived from large-scale genotyping, and neighborhood deprivation, defined using 2000 census-tract-level Neighborhood Deprivation Index (NDI) score. Main Outcomes and Measures: Outcomes of interest were prostate cancer and all-cause mortality. Results: Among a total of 1469 participants (mean [SD] age, 64.96 [7.95] years), there were 736 self-identified Black and 733 White men, and the mean (range) proportion of West African genetic ancestry was 0.27 (0.04-0.84) among participants residing in areas with low levels of deprivation and 0.48 (0.07-0.83) among participants residing in areas with high levels of deprivation. Multivariable logistic regression analysis revealed a significant multiplicative interaction of West African genetic ancestry and neighborhood deprivation with the odds of a prostate cancer diagnosis (P for interaction = .02). Among individuals living in neighborhoods with high NDI scores, West African genetic ancestry was associated with increased odds of a prostate cancer diagnosis (age-adjusted odds ratio [OR], 1.98; 95% CI, 1.23-3.19). In contrast, West African genetic ancestry was associated with reduced odds of this diagnosis among individuals residing in areas with medium to low levels of deprivation (age-adjusted OR, 0.22; 95% CI, 0.11-0.44). There was no significant multiplicative interaction between West African genetic ancestry and neighborhood deprivation for all-cause mortality (P for interaction = .44). The positive association of neighborhood deprivation with prostate cancer was independent of West African genetic ancestry (age- and West African ancestry-adjusted OR, 1,70; 95% CI, 1.50-1.94). Conclusions and Relevance: This case-control study of men with West African and European ancestry found that West African genetic ancestry was associated with increased odds of prostate cancer among males who resided in neighborhoods with high deprivation but lower odds in more affluent neighborhoods. Thus, neighborhood environments may play a critical role in defining how genetic ancestry modulates prostate cancer risk.


Asunto(s)
Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/mortalidad , Estudios de Casos y Controles , Persona de Mediana Edad , Anciano , Baltimore/epidemiología , Características de la Residencia/estadística & datos numéricos , África Occidental , Población Blanca/estadística & datos numéricos , Población Blanca/genética , Características del Vecindario/estadística & datos numéricos , Población Negra/estadística & datos numéricos , Población Negra/genética , Negro o Afroamericano/estadística & datos numéricos , Negro o Afroamericano/genética , Factores de Riesgo
3.
Genes (Basel) ; 15(8)2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39202458

RESUMEN

Human populations have interacted throughout history, and a considerable portion of modern human populations show evidence of admixture. Local ancestry inference (LAI) is focused on detecting the genetic ancestry of chromosomal segments in admixed individuals and has wide applications. In this work, we proposed a new LAI method based on population-specific single-nucleotide polymorphisms (SNPs) and applied it in the analysis of admixed populations in the 1000 Genomes Project (1KGP). Based on population-specific SNPs in a sliding window, we computed local ancestry information vectors, which are moment estimators of local ancestral proportions, for two haplotypes of an admixed individual and inferred the local ancestral origins. Then we used African (AFR), East Asian (EAS), European (EUR) and South Asian (SAS) populations from the 1KGP and indigenous American (AMR) populations from the Human Genome Diversity Project (HGDP) as reference populations and conducted the proposed LAI analysis on African American populations and American populations in the 1KGP. The results were compared with those obtained by RFMix, G-Nomix and FLARE. We demonstrated that the existence of alleles in a chromosomal region that are specific to a particular reference population and the absence of alleles specific to the other reference populations provide reasonable evidence for determining the ancestral origin of the region. Contemporary AFR, AMR and EUR populations approximate ancestral populations of the admixed populations well, and the results from RFMix, G-Nomix and FLARE largely agree with those from the Ancestral Spectrum Analyzer (ASA), in which the proposed method was implemented. When admixtures are ancient and contemporary reference populations do not satisfactorily approximate ancestral populations, the performances of RFMix, G-Nomix and FLARE deteriorate with increased error rates and fragmented chromosomal segments. In contrast, our method provides fair results.


Asunto(s)
Genética de Población , Genoma Humano , Polimorfismo de Nucleótido Simple , Humanos , Pueblo Asiatico/genética , Población Negra/genética , Genética de Población/métodos , Haplotipos , Proyecto Genoma Humano , Población Blanca/genética , Pueblos Indígenas/genética
4.
Nat Commun ; 15(1): 7307, 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39181874

RESUMEN

Sub-equatorial Africa is today inhabited predominantly by Bantu-speaking groups of Western African descent who brought agriculture to the Luangwa valley in eastern Zambia ~2000 years ago. Before their arrival the area was inhabited by hunter-gatherers, who in many cases were subsequently replaced, displaced or assimilated. In Zambia, we know little about the genetic affinities of these hunter-gatherers. We examine ancestry of two isolated communities in Zambia, known as BaTwa and possible descendants of recent hunter-gatherers. We genotype over two million genome-wide SNPs from two BaTwa populations (total of 80 individuals) and from three comparative farming populations to: (i) determine if the BaTwa carry genetic links to past hunter-gatherer-groups, and (ii) characterise the genetic affinities of past Zambian hunter-gatherer-groups. The BaTwa populations do harbour a hunter-gatherer-like genetic ancestry and Western African ancestry. The hunter-gatherer component is a unique local signature, intermediate between current-day Khoe-San ancestry from southern Africa and central African rainforest hunter-gatherer ancestry.


Asunto(s)
Población Negra , Genética de Población , Polimorfismo de Nucleótido Simple , Humanos , Agricultura , Población Negra/genética , Genotipo , Zambia
5.
Genome Med ; 16(1): 106, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39187845

RESUMEN

BACKGROUND: Cardiovascular diseases (CVD) are a major health concern in Africa. Improved identification and treatment of high-risk individuals can reduce adverse health outcomes. Current CVD risk calculators are largely unvalidated in African populations and overlook genetic factors. Polygenic scores (PGS) can enhance risk prediction by measuring genetic susceptibility to CVD, but their effectiveness in genetically diverse populations is limited by a European-ancestry bias. To address this, we developed models integrating genetic data and conventional risk factors to assess the risk of developing cardiometabolic outcomes in African populations. METHODS: We used summary statistics from a genome-wide association meta-analysis (n = 14,126) in African populations to derive novel genome-wide PGS for 14 cardiometabolic traits in an independent African target sample (Africa Wits-INDEPTH Partnership for Genomic Research (AWI-Gen), n = 10,603). Regression analyses assessed relationships between each PGS and corresponding cardiometabolic trait, and seven CVD outcomes (CVD, heart attack, stroke, diabetes mellitus, dyslipidaemia, hypertension, and obesity). The predictive utility of the genetic data was evaluated using elastic net models containing multiple PGS (MultiPGS) and reference-projected principal components of ancestry (PPCs). An integrated risk prediction model incorporating genetic and conventional risk factors was developed. Nested cross-validation was used when deriving elastic net models to enhance generalisability. RESULTS: Our African-specific PGS displayed significant but variable within- and cross- trait prediction (max.R2 = 6.8%, p = 1.86 × 10-173). Significantly associated PGS with dyslipidaemia included the PGS for total cholesterol (logOR = 0.210, SE = 0.022, p = 2.18 × 10-21) and low-density lipoprotein (logOR = - 0.141, SE = 0.022, p = 1.30 × 10-20); with hypertension, the systolic blood pressure PGS (logOR = 0.150, SE = 0.045, p = 8.34 × 10-4); and multiple PGS associated with obesity: body mass index (max. logOR = 0.131, SE = 0.031, p = 2.22 × 10-5), hip circumference (logOR = 0.122, SE = 0.029, p = 2.28 × 10-5), waist circumference (logOR = 0.013, SE = 0.098, p = 8.13 × 10-4) and weight (logOR = 0.103, SE = 0.029, p = 4.89 × 10-5). Elastic net models incorporating MultiPGS and PPCs significantly improved prediction over MultiPGS alone. Models including genetic data and conventional risk factors were more predictive than conventional risk models alone (dyslipidaemia: R2 increase = 2.6%, p = 4.45 × 10-12; hypertension: R2 increase = 2.6%, p = 2.37 × 10-13; obesity: R2 increase = 5.5%, 1.33 × 10-34). CONCLUSIONS: In African populations, CVD and associated cardiometabolic trait prediction models can be improved by incorporating ancestry-aligned PGS and accounting for ancestry. Combining PGS with conventional risk factors further enhances prediction over traditional models based on conventional factors. Incorporating data from target populations can improve the generalisability of international predictive models for CVD and associated traits in African populations.


Asunto(s)
Población Negra , Enfermedades Cardiovasculares , Estudio de Asociación del Genoma Completo , Herencia Multifactorial , Humanos , Enfermedades Cardiovasculares/genética , Población Negra/genética , Masculino , Femenino , Factores de Riesgo , Persona de Mediana Edad , Predisposición Genética a la Enfermedad , Adulto , Polimorfismo de Nucleótido Simple , Factores de Riesgo Cardiometabólico
6.
Pharmacogenomics J ; 24(4): 23, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090078

RESUMEN

The influence of genetic variants related to opioid use disorder (OUD) was evaluated using multiple logistic regression analysis in self-reported assigned African American/Afro-Caribbean and European biogeographical ancestry groups (BGAGs) and by sex. From a sample size of 1301 adult patients (>18 years of age) seen in emergency departments of three medical centers in Ohio, six variants were found to be associated with OUD. Two of the variants, rs2740574 (CYP3A4) and rs324029 (DRD3), were included in the analysis having met criteria of at least five subjects for each BGAG, variant carrier status, and OUD status combinations. Variant carriers in the African/Afro-Caribbean BGAG had slightly lower predicted probabilities of OUD. Variant carriers in the European BGAG had slightly higher predicted probabilities of OUD. Relative to sex, all the six variants met evaluation criteria (five subjects for all sex, variant, and OUD status combinations). No statistically significant interactions were found between a given variant, BGAGs and sex. Findings suggest variant testing relative to OUD risk can be applied across BGAGs and sex, however, studies in larger populations are needed.


Asunto(s)
Alelos , Negro o Afroamericano , Trastornos Relacionados con Opioides , Población Blanca , Humanos , Masculino , Femenino , Trastornos Relacionados con Opioides/genética , Adulto , Negro o Afroamericano/genética , Población Blanca/genética , Autoinforme , Persona de Mediana Edad , Región del Caribe , Predisposición Genética a la Enfermedad/genética , Citocromo P-450 CYP3A/genética , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo , Población Negra/genética
7.
Science ; 385(6709): 595-599, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39116239

RESUMEN

With vision and a big personality, Christian Happi has built a world-class genomics center so Africans can help Africa.


Asunto(s)
Población Negra , Genómica , Humanos , África , Población Negra/genética
8.
Gene ; 931: 148854, 2024 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-39147113

RESUMEN

Ancestrally admixed populations are underrepresented in genetic studies of complex diseases, which are still dominated by European-descent populations. This is relevant not only from a representation standpoint but also because of admixed populations' unique features, including being enriched for rare variants, for which effect sizes are disproportionately larger than common polymorphisms. Furthermore, results from these populations may be generalizable to other populations. The South African Cape Coloured (SACC) population is genetically admixed and has one of the highest prevalences of fetal alcohol spectrum disorders (FASD) worldwide. We profiled its admixture and examined associations between ancestry profiles and FASD outcomes using two longitudinal birth cohorts (N=308 mothers, 280 children) designed to examine effects of prenatal alcohol exposure on development. Participants were genotyped via MEGAex array to capture common and rare variants. Rare variants were overrepresented in our SACC cohorts, with numerous polymorphisms being monomorphic in other reference populations (e.g., ∼30,000 and âˆ¼ 221,000 variants in gnomAD European and Asian populations, respectively). The cohorts showed global African (51 %; Bantu and San); European (26 %; Northern/Western); South Asian (18 %); and East Asian (5 %; largely Southern regions) ancestries. The cohorts exhibited high rates of homozygosity (6 %), with regions of homozygosity harboring more deleterious variants when lying within African local-ancestry genomic segments. Both maternal and child ancestry profiles were associated with higher FASD risk, and maternal and child ancestry-by-prenatal alcohol exposure interaction effects were seen on child cognition. Our findings indicate that the SACC population may be a valuable asset to identify novel disease-associated genetic loci for FASD and other diseases.


Asunto(s)
Trastornos del Espectro Alcohólico Fetal , Humanos , Trastornos del Espectro Alcohólico Fetal/genética , Trastornos del Espectro Alcohólico Fetal/epidemiología , Femenino , Sudáfrica/epidemiología , Masculino , Embarazo , Población Negra/genética , Adulto , Niño , Polimorfismo de Nucleótido Simple , Predisposición Genética a la Enfermedad , Población Blanca/genética
9.
Pharmacogenomics ; 25(7): 329-341, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39109483

RESUMEN

Calcineurin inhibitors (CNIs) are the mainstay of immunosuppression in kidney transplantation. Interpatient variability in the disposition of calcineurin inhibitors is a well-researched phenomenon and has a well-established genetic contribution. There is great diversity in the makeup of African genomes, but very little is known about the pharmacogenetics of CNIs and transplant outcomes. This review focuses on genetic variants of calcineurin inhibitors' metabolizing enzymes (CYP3A4, CYP3A5), related molecules (POR, PPARA) and membrane transporters involved in the metabolism of calcineurin inhibitors. Given the genetic diversity across the African continent, it is imperative to generate pharmacogenetic data, especially in the era of personalized medicine and emphasizes the need for studies specific to African populations. The study of allelic variants in populations where they have greater frequencies will help answer questions regarding their impact. We aim to fill the knowledge gaps by reviewing existing research and highlighting areas where African research can contribute.


Research on the pharmacogenetics of calcineurin inhibitors in kidney transplant recipients is truly wanting in data from the African continent. Given Africa's vast genetic diversity, it is necessary to intensify efforts to generate data from Africa in this field.


Asunto(s)
Inhibidores de la Calcineurina , Inmunosupresores , Trasplante de Riñón , Farmacogenética , Humanos , Inhibidores de la Calcineurina/uso terapéutico , Trasplante de Riñón/tendencias , Farmacogenética/métodos , Inmunosupresores/uso terapéutico , Receptores de Trasplantes , Población Negra/genética , Citocromo P-450 CYP3A/genética , África
10.
Alzheimers Dement ; 20(8): 5247-5261, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38958117

RESUMEN

INTRODUCTION: Despite a two-fold risk, individuals of African ancestry have been underrepresented in Alzheimer's disease (AD) genomics efforts. METHODS: Genome-wide association studies (GWAS) of 2,903 AD cases and 6,265 controls of African ancestry. Within-dataset results were meta-analyzed, followed by functional genomics analyses. RESULTS: A novel AD-risk locus was identified in MPDZ on chromosome (chr) 9p23 (rs141610415, MAF = 0.002, p = 3.68×10-9). Two additional novel common and nine rare loci were identified with suggestive associations (P < 9×10-7). Comparison of association and linkage disequilibrium (LD) patterns between datasets with higher and lower degrees of African ancestry showed differential association patterns at chr12q23.2 (ASCL1), suggesting that this association is modulated by regional origin of local African ancestry. DISCUSSION: These analyses identified novel AD-associated loci in individuals of African ancestry and suggest that degree of African ancestry modulates some associations. Increased sample sets covering as much African genetic diversity as possible will be critical to identify additional loci and deconvolute local genetic ancestry effects. HIGHLIGHTS: Genetic ancestry significantly impacts risk of Alzheimer's Disease (AD). Although individuals of African ancestry are twice as likely to develop AD, they are vastly underrepresented in AD genomics studies. The Alzheimer's Disease Genetics Consortium has previously identified 16 common and rare genetic loci associated with AD in African American individuals. The current analyses significantly expand this effort by increasing the sample size and extending ancestral diversity by including populations from continental Africa. Single variant meta-analysis identified a novel genome-wide significant AD-risk locus in individuals of African ancestry at the MPDZ gene, and 11 additional novel loci with suggestive genome-wide significance at p < 9×10-7. Comparison of African American datasets with samples of higher degree of African ancestry demonstrated differing patterns of association and linkage disequilibrium at one of these loci, suggesting that degree and/or geographic origin of African ancestry modulates the effect at this locus. These findings illustrate the importance of increasing number and ancestral diversity of African ancestry samples in AD genomics studies to fully disentangle the genetic architecture underlying AD, and yield more effective ancestry-informed genetic screening tools and therapeutic interventions.


Asunto(s)
Enfermedad de Alzheimer , Población Negra , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Desequilibrio de Ligamiento , Polimorfismo de Nucleótido Simple , Humanos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/etnología , Predisposición Genética a la Enfermedad/genética , Población Negra/genética , Polimorfismo de Nucleótido Simple/genética , Femenino , Masculino , Anciano
11.
Afr Health Sci ; 24(1): 307-312, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38962329

RESUMEN

Introduction: Pharmacogenetic markers, such as the ATP Binding Cassette (ABCB1) and cytochrome P450 (CYP) 3A5 enzymes, play a crucial role in personalized medicine by influencing drug efficacy and toxicity based on individuals' or populations' genetic variations.This study aims to investigate the genetic polymorphisms of CYP3A5 (rs776746) and ABCB1 (rs1045642) in the West Algerian population and compare the genotypes and allelic distributions with those of various ethnic groups. Methods: The study involved 472 unrelated healthy subjects from the Western Algerian population. DNA genotyping was performed using TaqMan allelic discrimination assay. The variants in our population were compared to those in other ethnic groups available in the 1000 Genomes Project. Genotype and allele frequencies were calculated using the chi-square test and the Hardy-Weinberg equilibrium (HWE). Results: The minor allele frequencies were found to be 0.21 for CYP3A5 6986A and 0.34 for ABCB1 3435T. These frequencies were similar to those observed in North African populations, while notable differences were observed in comparison to certain Caucasian and African populations. Conclusion: The difference in the allelic and genotypic distribution of these polymorphisms emphasize the need for dose adjustments in drugs metabolized by CYP3A5 and transported by ABCB1 to optimize treatments outcomes.


Asunto(s)
Subfamilia B de Transportador de Casetes de Unión a ATP , Citocromo P-450 CYP3A , Frecuencia de los Genes , Genotipo , Polimorfismo de Nucleótido Simple , Humanos , Citocromo P-450 CYP3A/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Argelia , Masculino , Femenino , Adulto , Farmacogenética , Persona de Mediana Edad , Población Negra/genética , Alelos , Adulto Joven
12.
S Afr Med J ; 114(6): e1094, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-39041507

RESUMEN

BACKGROUND: Hereditary breast cancer is characterised by the presence of a pathogenic sequence variant passed from one generation to the next. These cancers are aggressive, develop early, and account for 5 - 10% of all breast cancer cases. In South Africa (SA), the common variants that predispose to hereditary breast cancer have been well documented among white patients and form part of screening panels during targeted testing. For non-white patients, common variants are not well understood, and as such, all populations are offered the same test optimised for white patients. This carries a risk of misdiagnosis, the consequences of which include recurrence and increased mortality. OBJECTIVES: To retrospectively describe genetic trends in the black African and Indian breast cancer patients from KwaZulu-Natal Province, SA. METHODS: We reviewed clinical and genetic data of breast cancer and high-risk patients who consulted at Inkosi Albert Luthuli Central Hospital between 2011 and 2021. Inclusion criteria were based on clinical and demographic characteristics as defined by SA clinical guidelines. RESULTS: Black African patients were young (mean 37.6 years, standard deviation 11.16) and had the majority of triple-negative tumours (37.5%). Indians represented 50% of bilateral breast cancers and of high-risk individuals. We identified 30 pathogenic BRCA1/2 sequence variants, four large genomic rearrangements and 13 variants of unknown significance. Twenty black patients carried 12, 13 white patients carried 4, 25 Indian patients carried 16, and 3 coloured patients carried 3 pathogenic sequence variants. The most frequent variants were BRCA2 c.5771_5774del, p.Ile1924fs among black patients, BRCA2 c.7934del, p.Arg2645fs among white patients, and BRCA2 c.8754+1G>A among Indian patients. None of the founder mutations common in white patients was reported in either black, Indian or coloured patients, which explains why black, Coloured and Indian SA patients consistently test negative during targeted screening. CONCLUSION: This study highlights unique genetic trends for SA populations and the need for more inclusive targeted tests that are optimal for these populations.


Asunto(s)
Proteína BRCA1 , Proteína BRCA2 , Población Negra , Neoplasias de la Mama , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Población Negra/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/etnología , Predisposición Genética a la Enfermedad , Mutación , Estudios Retrospectivos , Sudáfrica/epidemiología
13.
Am J Hum Genet ; 111(7): 1243-1251, 2024 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-38996465

RESUMEN

Population history-focused DNA and ancient DNA (aDNA) research in Africa has dramatically increased in the past decade, enabling increasingly fine-scale investigations into the continent's past. However, while international interest in human genomics research in Africa grows, major structural barriers limit the ability of African scholars to lead and engage in such research and impede local communities from partnering with researchers and benefitting from research outcomes. Because conversations about research on African people and their past are often held outside Africa and exclude African voices, an important step for African DNA and aDNA research is moving these conversations to the continent. In May 2023 we held the DNAirobi workshop in Nairobi, Kenya and here we synthesize what emerged most prominently in our discussions. We propose an ideal vision for population history-focused DNA and aDNA research in Africa in ten years' time and acknowledge that to realize this future, we need to chart a path connecting a series of "landmarks" that represent points of consensus in our discussions. These include effective communication across multiple audiences, reframed relationships and capacity building, and action toward structural changes that support science and beyond. We concluded there is no single path to creating an equitable and self-sustaining research ecosystem, but rather many possible routes linking these landmarks. Here we share our diverse perspectives as geneticists, anthropologists, archaeologists, museum curators, and educators to articulate challenges and opportunities for African DNA and aDNA research and share an initial map toward a more inclusive and equitable future.


Asunto(s)
ADN Antiguo , Genética de Población , Humanos , ADN Antiguo/análisis , África , Genómica , Población Negra/genética
14.
Genome Biol ; 25(1): 201, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080715

RESUMEN

BACKGROUND: North African human populations present a complex demographic scenario due to the presence of an autochthonous genetic component and population substructure, plus extensive gene flow from the Middle East, Europe, and sub-Saharan Africa. RESULTS: We conducted a comprehensive analysis of 364 genomes to construct detailed demographic models for the North African region, encompassing its two primary ethnic groups, the Arab and Amazigh populations. This was achieved through an Approximate Bayesian Computation with Deep Learning (ABC-DL) framework and a novel algorithm called Genetic Programming for Population Genetics (GP4PG). This innovative approach enabled us to effectively model intricate demographic scenarios, utilizing a subset of 16 whole genomes at > 30X coverage. The demographic model suggested by GP4PG exhibited a closer alignment with the observed data compared to the ABC-DL model. Both point to a back-to-Africa origin of North African individuals and a close relationship with Eurasian populations. Results support different origins for Amazigh and Arab populations, with Amazigh populations originating back in Epipaleolithic times, while GP4PG supports Arabization as the main source of Middle Eastern ancestry. The GP4PG model includes population substructure in surrounding populations (sub-Saharan Africa and Middle East) with continuous decaying gene flow after population split. Contrary to ABC-DL, the best GP4PG model does not require pulses of admixture from surrounding populations into North Africa pointing to soft splits as drivers of divergence in North Africa. CONCLUSIONS: We have built a demographic model on North Africa that points to a back-to-Africa expansion and a differential origin between Arab and Amazigh populations.


Asunto(s)
Genética de Población , Genoma Humano , Humanos , África del Norte , Población Negra/genética , Modelos Genéticos , Flujo Génico , Teorema de Bayes , Medio Oriente , Árabes/genética , Algoritmos , Pueblo Norteafricano
15.
Genes (Basel) ; 15(7)2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39062696

RESUMEN

Epidemiological studies frequently classify groups based on phenotypes like self-reported skin color/race, which inaccurately represent genetic ancestry and may lead to misclassification, particularly among individuals of multiracial backgrounds. This study aimed to characterize both global and local genome-wide genetic ancestries and to assess their relationship with self-reported skin color/race in an admixed population of Sao Paulo city. We analyzed 226,346 single-nucleotide polymorphisms from 841 individuals participating in the population-based ISA-Nutrition study. Our findings confirmed the admixed nature of the population, demonstrating substantial European, significant Sub-Saharan African, and minor Native American ancestries, irrespective of skin color. A correlation was observed between global genetic ancestry and self-reported color-race, which was more evident in the extreme proportions of African and European ancestries. Individuals with higher African ancestry tended to identify as Black, those with higher European ancestry tended to identify as White, and individuals with higher Native American ancestry were more likely to self-identify as Mixed, a group with diverse ancestral compositions. However, at the individual level, this correlation was notably weak, and no deviations were observed for specific regions throughout the individual's genome. Our findings emphasize the significance of accurately defining and thoroughly analyzing race and ancestry, especially within admixed populations.


Asunto(s)
Polimorfismo de Nucleótido Simple , Autoinforme , Pigmentación de la Piel , Humanos , Brasil , Pigmentación de la Piel/genética , Masculino , Femenino , Adulto , Población Blanca/genética , Población Urbana , Población Negra/genética , Grupos Raciales/genética , Persona de Mediana Edad , Genética de Población
16.
Sci Rep ; 14(1): 15653, 2024 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-38977763

RESUMEN

Despite their ancient past and high diversity, African populations are the least represented in human population genetic studies. In this study, uniparental markers (mtDNA and Y chromosome) were used to investigate the impact of sociocultural factors on the genetic diversity and inter-ethnolinguistic gene flow in the three major Nigerian groups: Hausa (n = 89), Yoruba (n = 135) and Igbo (n = 134). The results show a distinct history from the maternal and paternal perspectives. The three Nigerian groups present a similar substrate for mtDNA, but not for the Y chromosome. The two Niger-Congo groups, Yoruba and Igbo, are paternally genetically correlated with populations from the same ethnolinguistic affiliation. Meanwhile, the Hausa is paternally closer to other Afro-Asiatic populations and presented a high diversity of lineages from across Africa. When expanding the analyses to other African populations, it is observed that language did not act as a major barrier to female-mediated gene flow and that the differentiation of paternal lineages is better correlated with linguistic than geographic distances. The results obtained demonstrate the impact of patrilocality, a common and well-established practice in populations from Central-West Africa, in the preservation of the patrilineage gene pool and in the affirmation of identity between groups.


Asunto(s)
Cromosomas Humanos Y , ADN Mitocondrial , Flujo Génico , Variación Genética , Femenino , Humanos , Masculino , África Occidental , Población Negra/genética , Cromosomas Humanos Y/genética , ADN Mitocondrial/genética , Genética de Población , Haplotipos , Herencia Paterna , Pueblo Africano/genética
17.
Mamm Genome ; 35(3): 445-460, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38965090

RESUMEN

The demographic history of human populations in North Africa has been characterized by complex migration processes that have determined the current genetic structure of these populations. We examined the autosomal markers of eight sampled populations in northern Africa (Tunisia and Libya) to explore their genetic structure and to place them in a global context. We genotyped a set of 30 autosomal single-nucleotide polymorphisms (SNPs) extending 9.5 Mb and encompassing the 17q21 inversion region. Our data include 403 individuals from Tunisia and Libya. To put our populations in the global context, we analyzed our data in comparison with other populations, including those of the 1000 Genomes Project. To evaluate the data, we conducted genetic diversity, principal component, STRUCTURE, and haplotype analyses. The analysis of genetic composition revealed the genetic heterogeneity of North African populations. The principal component and STRUCTURE analyses converged and revealed the intermediate position of North Africans between Europeans and Asians. Haplotypic analysis demonstrated that the normal (H1) and inverted (H2) polymorphisms in the chromosome 17q21 region occur in North Africa at frequencies similar to those found in European and Southwest Asian populations. The results highlight the complex demographic history of North Africa, reflecting the influence of genetic flow from Europe and the Near East that dates to the prehistoric period. These gene flows added to demographic factors (inbreeding, endogamy), natural factors (topography, Sahara), and cultural factors that play a role in the emergence of the diverse and heterogeneous genetic structures of North African populations. This study contributes to a better understanding of the complex structure of North African populations.


Asunto(s)
Cromosomas Humanos Par 17 , Variación Genética , Genética de Población , Haplotipos , Polimorfismo de Nucleótido Simple , Humanos , Cromosomas Humanos Par 17/genética , África del Norte , Población Negra/genética , Túnez , Análisis de Componente Principal , Libia , Frecuencia de los Genes , Pueblo Norteafricano
18.
Int J Mol Sci ; 25(12)2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38928370

RESUMEN

Reactive oxygen species (ROS) participate in almost all disorders, including cancer. Many factors, including aging, a high-fat diet, a stressful lifestyle, smoking, infection, genetic mutations, etc., lead to elevated levels of ROS. Prostate cancer, the most prevalent type of cancer in senior American men and the second leading cause of cancer mortality in American men, results from chronic oxidative stress. The doubled incident rate as well as the doubled mortality numbers of prostate cancer have persisted in African Americans in comparison with Caucasian Americans and other racial groups, indicating a prostate cancer disparity in African American men. In this review, we mainly focus on the latest findings on ROS in prostate cancer development and progression within the last five years to update our understanding in this area, as several comprehensive literature reviews addressing oxidative stress and/or inflammation in prostate cancer before 2020 are available. In addition to other known factors such as socioeconomic disadvantage, cultural mistrust of the health care system, etc. that are long-existing in the African American group, we also summarize the latest evidence that demonstrated high systemic oxidative stress and inflammation in African Americans for their potential contribution to the racial prostate cancer disparity in this population.


Asunto(s)
Negro o Afroamericano , Estrés Oxidativo , Neoplasias de la Próstata , Especies Reactivas de Oxígeno , Humanos , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/epidemiología , Especies Reactivas de Oxígeno/metabolismo , Negro o Afroamericano/genética , Población Negra/genética , Disparidades en el Estado de Salud , Inflamación/metabolismo
20.
Nat Med ; 30(9): 2480-2488, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38918629

RESUMEN

Diabetes complications occur at higher rates in individuals of African ancestry. Glucose-6-phosphate dehydrogenase deficiency (G6PDdef), common in some African populations, confers malaria resistance, and reduces hemoglobin A1c (HbA1c) levels by shortening erythrocyte lifespan. In a combined-ancestry genome-wide association study of diabetic retinopathy, we identified nine loci including a G6PDdef causal variant, rs1050828 -T (Val98Met), which was also associated with increased risk of other diabetes complications. The effect of rs1050828 -T on retinopathy was fully mediated by glucose levels. In the years preceding diabetes diagnosis and insulin prescription, glucose levels were significantly higher and HbA1c significantly lower in those with versus without G6PDdef. In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, participants with G6PDdef had significantly higher hazards of incident retinopathy and neuropathy. At the same HbA1c levels, G6PDdef participants in both ACCORD and the Million Veteran Program had significantly increased risk of retinopathy. We estimate that 12% and 9% of diabetic retinopathy and neuropathy cases, respectively, in participants of African ancestry are due to this exposure. Across continentally defined ancestral populations, the differences in frequency of rs1050828 -T and other G6PDdef alleles contribute to disparities in diabetes complications. Diabetes management guided by glucose or potentially genotype-adjusted HbA1c levels could lead to more timely diagnoses and appropriate intensification of therapy, decreasing the risk of diabetes complications in patients with G6PDdef alleles.


Asunto(s)
Complicaciones de la Diabetes , Retinopatía Diabética , Estudio de Asociación del Genoma Completo , Deficiencia de Glucosafosfato Deshidrogenasa , Glucosafosfato Deshidrogenasa , Humanos , Glucosafosfato Deshidrogenasa/genética , Deficiencia de Glucosafosfato Deshidrogenasa/genética , Deficiencia de Glucosafosfato Deshidrogenasa/complicaciones , Deficiencia de Glucosafosfato Deshidrogenasa/epidemiología , Retinopatía Diabética/genética , Retinopatía Diabética/epidemiología , Complicaciones de la Diabetes/genética , Complicaciones de la Diabetes/epidemiología , Hemoglobina Glucada/metabolismo , Masculino , Femenino , Población Negra/genética , Polimorfismo de Nucleótido Simple , Persona de Mediana Edad , Glucemia/metabolismo
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