History Shaped the Geographic Distribution of Genomic Admixture on the Island of Puerto Rico

Via, Marc; Gignoux, Christopher R.; Roth, Lindsey A.; Fejerman, Laura; Galanter, Joshua; Choudhry, Shweta; Toro-Labrador, Gladys; Viera-Vera, Jorge; Oleksyk, Tarás K.; Beckman, Kenneth B.; Ziv, Elad; Risch, Neil; Burchard, Esteban G.; Martínez‐Cruzado, Juan Carlos

doi:10.1371/journal.pone.0016513

Cited by 87 publications

(99 citation statements)

References 35 publications

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“…The ancestry profiles for PR show a distribution where the European ancestry (EA) is the more prevalent (64%) followed by West African ancestry (WAA) (21%) and native ancestry (NA) (15%) [35–38]. FTO mutations have been associated with PCa in populations with high EA [39,40].…”

Section: Introductionmentioning

confidence: 99%

Impact of FTO SNPs rs9930506 and rs9939609 in Prostate Cancer Severity in a Cohort of Puerto Rican Men

Salgado-Montilla

Rodríguez-Cabán

Sánchez-García

et al. 2017

Can Res

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Background Obesity is prevalent in PR and has been associated with prostate cancer (PCa) mortality and aggressiveness. Polymorphisms (SNPs) rs9930506 and rs9939609 in the FTO gene have been associated with both obesity and PCa. The aim of this work was to ascertain whether the presence of these SNPs is associated with PCa risk and severity in a cohort of Puerto Rican men. Methods and findings The study population consisted of 513 Puerto Rican men age ranging from 40–79 years old who underwent radical prostatectomy (RP) as the first treatment for PCa and 128 healthy Puerto Rican men age ranging from 40–79 years old. Genomic DNA (gDNA) was extracted and SNPs were determined by Real-Time PCR. PCa severity was defined based on RP stage and Gleason Score. The relationship of FTO SNPs with demographic, clinical characteristics, PCa status and PCa severity were assessed. Logistic regression models with a 95% confidence interval (CI) determined SNPs interaction with PCa risk and severity odds ratio (ORs). Results and discussion BMI, age and PSA were considered as confounders. Hardy-Weinberg equilibrium was present for both SNPs. The heterozygous forms (A/G; T/A) were the most prevalent genotypes and the frequency of alleles and genotypes for both SNPs agreed with those published in 1000 genomes. Results suggest an inverse association between the mutated rs9939609 and the risk of having PCa (OR: 0.53, 95% CI: 0.31–0.92) and a positive association with overweight (OR: 1.05, 95% CI: 0.68–1.62). Importantly, among the cases that were overweight, those with mutated rs9939609 had a greater chance of high severity PCa (OR: 1.39, 95% CI: 0.84–2.32) although these results were not statistical significant upon adjustment. Limitations of the study were the relatively small cohort and lack of access to the weight history of all our subjects. Conclusion Results offer a research line to be followed with an expanded number of subjects that may provide a better statistical significance, to unravel the high mortality rate in this population.

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Section: Introductionmentioning

confidence: 99%

Impact of FTO SNPs rs9930506 and rs9939609 in Prostate Cancer Severity in a Cohort of Puerto Rican Men

Salgado-Montilla

Rodríguez-Cabán

Sánchez-García

et al. 2017

Can Res

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“…Most Puerto Ricans are racially admixed, with various proportions of European, African, and Native American ancestry (12). We hypothesized that vitamin D insufficiency is common and associated with severe asthma exacerbations in Puerto Rican children, and that this association is independent of African racial ancestry, time spent outdoors, atopy, and reported dietary intake of vitamin D. To test this hypothesis, we examined the relationship between vitamin D insufficiency and severe asthma exacerbations in 560 Puerto Rican children with (n ¼ 287) and without (n ¼ 273) asthma living in San Juan, Puerto Rico.…”

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confidence: 99%

Vitamin D Insufficiency and Severe Asthma Exacerbations in Puerto Rican Children

Brehm

Acosta‐Pérez

Klei³

et al. 2012

Am J Respir Crit Care Med

198

168

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Rationale: Vitamin D insufficiency (a serum 25(OH)D ,30 ng/ml) has been associated with severe asthma exacerbations, but this could be explained by underlying racial ancestry or disease severity. Little is known about vitamin D and asthma in Puerto Ricans. Objectives: To examine whether vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, and time outdoors. Methods: A cross-sectional study was conducted of 560 children ages 6-14 years with (n ¼ 287) and without (n ¼ 273) asthma in San Juan, Puerto Rico. We measured plasma vitamin D and estimated the percentage of African racial ancestry among participants using genomewide genotypic data. We tested whether vitamin D insufficiency is associated with severe asthma exacerbations, lung function, or atopy (greater than or equal to one positive IgE to allergens) using logistic or linear regression. Multivariate models were adjusted for African ancestry, time outdoors, atopy, and other covariates. Measurements and Main Results: Vitamin D insufficiency was common in children with (44%) and without (47%) asthma. In multivariate analyses, vitamin D insufficiency was associated with higher odds of greater than or equal to one severe asthma exacerbation in the prior year (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.5-4.9; P ¼ 0.001) and atopy, and a lower FEV 1 /FVC in cases. After stratification by atopy, the magnitude of the association between vitamin D insufficiency and severe exacerbations was greater in nonatopic (OR, 6.2; 95% CI, 2-21.6; P ¼ 0.002) than in atopic (OR, 2; 95% CI, 1-4.1; P ¼ 0.04) cases. Conclusions: Vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, or markers of disease severity or control.Keywords: vitamin D; asthma exacerbations; Puerto Ricans; childhood Vitamin D insufficiency (a serum level of 25(OH)D ,30 ng/ml) is common among children in the United States mainland. For example, a nationwide study of 2,759 U.S. children ages 6-11 years found vitamin D insufficiency in approximately 62% of nonHispanic whites, approximately 86% of Hispanics, and approximately 96% of non-Hispanic blacks (1). Vitamin D insufficiency has been associated with increased asthma morbidity, particularly severe disease exacerbations, in observational studies of children of school age in Costa Rica (2) and North America (3).Although current evidence from observational (2-5) and experimental studies (6-9) suggests that vitamin D insufficiency leads to severe asthma exacerbations or increased asthma morbidity in childhood (10), no study of vitamin D and asthma morbidity has accounted for objectively assessed racial ancestry and time spent outdoors. This is critical to exclude whether vitamin D insufficiency is associated with severe asthma exacerbations or asthma morbidity through "reverse causation" (e.g., more severe asthma leading to reduced time outdoors and thus decreased exposure to sunlight ...

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“…These and other similarly admixed groups are frequently studied, most often to map variants responsible for disease, detect natural selection, and infer population history. [1][2][3][4] Importantly, many local US populations sustain admixture between substantially less divergent sources, often between a variety of European nationalities. The population genetic consequences of this admixture dynamic are seldom examined.…”

Section: Introductionmentioning

confidence: 99%

Genetic ancestry inference using support vector machines, and the active emergence of a unique American population

2012

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We use genotype data from the Marshfield Clinical Research Foundation Personalized Medicine Research Project to investigate genetic similarity and divergence between Europeans and the sampled population of European Americans in Central Wisconsin, USA. To infer recent genetic ancestry of the sampled Wisconsinites, we train support vector machines (SVMs) on the positions of Europeans along top principal components (PCs). Our SVM models partition continent-wide European genetic variance into eight regional classes, which is an improvement over the geographically broader categories of recent ancestry reported by personal genomics companies. After correcting for misclassification error associated with the SVMs (o10%, in all cases), we observe a 414% discrepancy between insular ancestries reported by Wisconsinites and those inferred by SVM. Values of F ST as well as Mantel tests for correlation between genetic and European geographic distances indicate minimal divergence between Europe and the local Wisconsin population. However, we find that individuals from the Wisconsin sample show greater dispersion along higher-order PCs than individuals from Europe. Hypothesizing that this pattern is characteristic of nascent divergence, we run computer simulations that mimic the recent peopling of Wisconsin. Simulations corroborate the pattern in higher-order PCs, demonstrate its transient nature, and show that admixture accelerates the rate of divergence between the admixed population and its parental sources relative to drift alone. Together, empirical and simulation results suggest that genetic divergence between European source populations and European Americans in Central Wisconsin is subtle but already under way.

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History Shaped the Geographic Distribution of Genomic Admixture on the Island of Puerto Rico

Cited by 87 publications

References 35 publications

Impact of FTO SNPs rs9930506 and rs9939609 in Prostate Cancer Severity in a Cohort of Puerto Rican Men

Impact of FTO SNPs rs9930506 and rs9939609 in Prostate Cancer Severity in a Cohort of Puerto Rican Men

Vitamin D Insufficiency and Severe Asthma Exacerbations in Puerto Rican Children

Genetic ancestry inference using support vector machines, and the active emergence of a unique American population

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