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Genetic comparison of sickle cell anaemia cohorts from Brazil and the United States reveals high levels of divergence.

ABSTRACT: Genetic analysis of admixed populations raises special concerns with regard to study design and data processing, particularly to avoid population stratification biases. The point mutation responsible for sickle cell anaemia codes for a variant hemoglobin, sickle hemoglobin or HbS, whose presence drives the pathophysiology of disease. Here we propose to explore ancestry and population structure in a genome-wide study with particular emphasis on chromosome 11 in two SCA admixed cohorts obtained from urban populations of Brazil (Pernambuco and São Paulo) and the United States (Pennsylvania). Ancestry inference showed different proportions of European, African and American backgrounds in the composition of our samples. Brazilians were more admixed, had a lower African background (43% vs. 78% on the genomic level and 44% vs. 76% on chromosome 11) and presented a signature of positive selection and Iberian introgression in the HbS region, driving a high differentiation of this locus between the two cohorts. The genetic structures of the SCA cohorts from Brazil and US differ considerably on the genome-wide, chromosome 11 and HbS mutation locus levels.

SUBMITTER: Cruz PRS

PROVIDER: S-EPMC6659681 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Genetic comparison of sickle cell anaemia cohorts from Brazil and the United States reveals high levels of divergence.

Cruz Pedro R S PRS Ananina Galina G Gil-da-Silva-Lopes Vera Lucia VL Simioni Milena M Menaa Farid F Bezerra Marcos A C MAC Domingos Igor F IF Araújo Aderson S AS Pellegrino Renata R Hakonarson Hakon H Costa Fernando F FF de Melo Mônica Barbosa MB

Scientific reports 20190726 1

Genetic analysis of admixed populations raises special concerns with regard to study design and data processing, particularly to avoid population stratification biases. The point mutation responsible for sickle cell anaemia codes for a variant hemoglobin, sickle hemoglobin or HbS, whose presence drives the pathophysiology of disease. Here we propose to explore ancestry and population structure in a genome-wide study with particular emphasis on chromosome 11 in two SCA admixed cohorts obtained fr ...[more]

PMID: 31350437

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Project description:IntroductionCharacterizing smoking history patterns summarizes life course exposure for birth cohorts, essential for evaluating the impact of tobacco control on health. Limited attention has been given to patterns among African Americans.MethodsLife course smoking histories of African Americans and whites were estimated beginning with the 1890 birth cohort. Estimates of smoking initiation and cessation probabilities, and intensity can be used as a baseline for studying smoking intervention strategies that target smoking exposure. US National Health Interview Surveys conducted from 1965 to 2012 yielded cross-sectional information on current smoking behavior among African Americans and whites. Additional detail for smokers including age at initiation, age at cessation and smoking intensity were available in some surveys and these were used to construct smoking histories for participants up to the date that they were interviewed. Age-period-cohort models with constrained natural splines provided estimates of current, former and never-smoker prevalence in cohorts beginning in 1890.ResultsThis approach yielded yearly estimates of initiation, cessation and smoking intensity by age for each birth cohort. Smoking initiation probabilities tend to be lower among African Americans compared to whites, and cessation probabilities also were generally lower. Higher initiation leads to higher smoking prevalence among whites in younger ages, but lower cessation leads to higher prevalence at older ages in blacks, when adverse health effects of smoking become most apparent.ConclusionsThese estimates provide a summary that can be used to better understand the effects of changes in smoking behavior following publication of the Surgeon General's Report in 1964.ImplicationsA novel method of estimating smoking histories was applied to data from the National Health Interview Surveys, which provided an extensive summary of the smoking history in this population following publication of the Surgeon General's Report in 1964. The results suggest that some of the existing disparities in smoking-related disease may be due to the lower cessation rates in African Americans compared to whites. However, the number of cigarettes smoked is also lower among African Americans. Further work is needed to determine mechanisms by which smoking duration and intensity can account for racial disparities in smoking-related diseases.

Project description:BackgroundTransfusion complicates a significant proportion of births in the United States, and Black women have greater prevalence of transfusion at delivery than White women. Antepartum anaemia, a risk factor for peripartum transfusion, is more common among Black women than White women. We aimed to describe the racial distribution of antepartum anaemia in three national datasets and to evaluate the peripartum transfusion rate and characteristics of transfusion recipients, to investigate disparities in haemostatic outcomes.Material and methodsWe performed a retrospective analysis of Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network Cesarean Registry (CR), NICHD Consortium on Safe Labor Registry (CSL), and a cohort of deliveries at Universal Health Services hospitals (UHS). Univariable associations and multivariable logistic regressions were calculated between race, anaemia and transfusion. Covariates included age, parity, smoking, body mass index, type of insurance, and delivery mode.ResultsWe included n=56,964 deliveries from CR (28% Black), 87,465 from UHS (12% Black), and 140,324 from CSL (24% Black). Anaemia prevalence was 8% in CR, 7% in UHS, and 13% in CSL. Anaemia was more common among Black patients (ORs 2.52, 2.61, and 1.48 respectively) and was associated with transfusion in all databases (ORs 6.46 [95% CI 5.78-7.22]; 5.79 [4.74-7.27]; 1.27 [1.18-1.37] respectively). After adjusting for covariates, Black patients had greater odds of transfusion than non-Black patients in CR (aOR 1.32 [1.16-1.50]), but not in UHS or CSL (aORs 1.19 [0.89-1.59] and 0.40 [0.36-0.44] respectively).DiscussionIn our retrospective cohort study using three US registries, we emphasized the link between anaemia and transfusion. Although anaemia was more prevalent among Black patients, the race-transfusion relationship differed between databases, indicating other unexplored factors are involved.

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Genetic comparison of sickle cell anaemia cohorts from Brazil and the United States reveals high levels of divergence.

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Genetic comparison of sickle cell anaemia cohorts from Brazil and the United States reveals high levels of divergence.

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