Dataset Information

Investigation of the locus near MC4R with childhood obesity in Americans of European and African ancestry.

ABSTRACT: Recently a modest, but consistently, replicated association was demonstrated between obesity and the single-nucleotide polymorphism (SNP), rs17782313, 3' of the MC4R locus as a consequence of a meta-analysis of genome-wide association (GWA) studies of the disease in white populations. We investigated the association in the context of the childhood form of the disease utilizing data from our ongoing GWA study in a cohort of 728 European-American (EA) obese children (BMI > or =95th percentile) and 3,960 EA controls (BMI <95th percentile), as well as 1,008 African-American (AA) obese children and 2,715 AA controls. rs571312, rs10871777, and rs476828 (perfect surrogates for rs17782313) yielded odds ratios in the EA cohort of 1.142 (P = 0.045), 1.137 (P = 0.054), and 1.145 (P = 0.042); however, there was no significant association with these SNPs in the AA cohort. When investigating all 30 SNPs present on the Illumina BeadChip at this locus, again there was no evidence for association in AA cases when correcting for the number of tests employed. As such, variants 3' to the MC4R locus present on the genotyping platform utilized confer a similar magnitude of risk of obesity in white children as to their adult white counterparts but this observation did not extend to AAs.

SUBMITTER: Grant SF

PROVIDER: S-EPMC2860794 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Investigation of the locus near MC4R with childhood obesity in Americans of European and African ancestry.

Grant Struan F A SF Bradfield Jonathan P JP Zhang Haitao H Wang Kai K Kim Cecilia E CE Annaiah Kiran K Santa Erin E Glessner Joseph T JT Thomas Kelly K Garris Maria M Frackelton Edward C EC Otieno F George FG Shaner Julie L JL Smith Ryan M RM Imielinski Marcin M Chiavacci Rosetta M RM Li Mingyao M Berkowitz Robert I RI Hakonarson Hakon H

Obesity (Silver Spring, Md.) 20090305 7

Recently a modest, but consistently, replicated association was demonstrated between obesity and the single-nucleotide polymorphism (SNP), rs17782313, 3' of the MC4R locus as a consequence of a meta-analysis of genome-wide association (GWA) studies of the disease in white populations. We investigated the association in the context of the childhood form of the disease utilizing data from our ongoing GWA study in a cohort of 728 European-American (EA) obese children (BMI > or =95th percentile) and ...[more]

PMID: 19265794

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Project description:BackgroundFamily history and African-American race are important risk factors for both prostate cancer (CaP) incidence and aggressiveness. When studying complex diseases such as CaP that have a heritable component, chances of finding true disease susceptibility alleles can be increased by accounting for genetic ancestry within the population investigated. Race, ethnicity and ancestry were studied in a geographically diverse cohort of men with newly diagnosed CaP.MethodsIndividual ancestry (IA) was estimated in the population-based North Carolina and Louisiana Prostate Cancer Project (PCaP), a cohort of 2,106 incident CaP cases (2063 with complete ethnicity information) comprising roughly equal numbers of research subjects reporting as Black/African American (AA) or European American/Caucasian/Caucasian American/White (EA) from North Carolina or Louisiana. Mean genome wide individual ancestry estimates of percent African, European and Asian were obtained and tested for differences by state and ethnicity (Cajun and/or Creole and Hispanic/Latino) using multivariate analysis of variance models. Principal components (PC) were compared to assess differences in genetic composition by self-reported race and ethnicity between and within states.ResultsMean individual ancestries differed by state for self-reporting AA (p = 0.03) and EA (p = 0.001). This geographic difference attenuated for AAs who answered "no" to all ethnicity membership questions (non-ethnic research subjects; p = 0.78) but not EA research subjects, p = 0.002. Mean ancestry estimates of self-identified AA Louisiana research subjects for each ethnic group; Cajun only, Creole only and both Cajun and Creole differed significantly from self-identified non-ethnic AA Louisiana research subjects. These ethnicity differences were not seen in those who self-identified as EA.ConclusionsMean IA differed by race between states, elucidating a potential contributing factor to these differences in AA research participants: self-reported ethnicity. Accurately accounting for genetic admixture in this cohort is essential for future analyses of the genetic and environmental contributions to CaP.

Project description:BackgroundPoor birth outcomes such as preterm birth/delivery disproportionately affect African Americans compared to White individuals. Reasons for this disparity are likely multifactorial, and include prenatal psychosocial stressors, and attendant increased lipid peroxidation; however, empirical data linking psychosocial stressors during pregnancy to oxidative status are limited.MethodsWe used established scales to measure five psychosocial stressors. Maternal adverse childhood experiences, financial stress, social support, anxiety, and depression were measured among 50 African American and White pregnant women enrolled in the Stress and Health in Pregnancy cohort. Liquid chromatography-tandem mass spectrometry was used to measure biomarkers of oxidative stress (four urinary F2-isoprostane isomers), to estimate oxidative status. Linear regression models were used to evaluate associations between psychosocial stressors, prenatal oxidative status and preterm birth.ResultsAfter adjusting for maternal obesity, gestational diabetes, and cigarette smoking, African American women with higher oxidative status were more likely to report higher maternal adverse childhood experience scores (β = 0.16, se = 1.07, p-value = 0.024) and depression scores (β = 0.05, se = 0.02, p = 0.014). Higher oxidative status was also associated with lower gestational age at birth (β = -0.13, se = 0.06, p = 0.04) in this population. These associations were not apparent in Whites. However, none of the cross-product terms for race/ethnicity and social stressors reached statistical significance (p > 0.05).ConclusionWhile the small sample size limits inference, our novel data suggest that psychosocial stressors may contribute significantly to oxidative stress during pregnancy, and preterm birth or delivery African Americans. If replicated in larger studies, these findings would support oxidative stress reduction using established dietary or pharmacological approaches present a potential avenue to mitigate adverse effects of psychosocial stressors on birth outcomes.

Project description:Translational Relevance Historically, African Americans have been underrepresented in clinical cancer research. Diversity helps to ensure equal access to new cancer therapies and better treatment for everyone. Cancer research is increasingly focused on classifying patients according to molecular profiles for particular groups. We provide a detailed molecular analysis from paired NSCLC tissues that identified differential coding and noncoding RNA expression in NSCLC from African Americans (AA) and European Americans (EA). Similar to other tumor types, we determined that race-enriched gene and microRNA expression signatures suggest a more aggressive disease in African Americans. Based on predicted drug resistance to adjuvant chemotherapies, AA may not equally benefit from the same range of clinical drugs as EA. Our findings provide a rationale for integrating coding and noncoding transcriptome profiles, along with clinical, demographic, and genomic data, when determining treatment options. Abstract Purpose: To determine if racial differences in gene and microRNA expression translates to differences in lung tumor biology with clinical relevance in African Americans (AA) and European Americans (EA). Experimental Design: The NCI-Maryland Case Control Study includes seven Baltimore City hospitals and is overrepresented with AA patients (~40%). Patients that underwent curative NSCLC surgery between 1998 and 2014 were enrolled. Comparative molecular profiling used mRNA (n = 22 AAs and n = 19 EAs) and microRNA (n = 42 AAs and n = 55 EAs) expression arrays to track differences in paired fresh frozen normal tissues and lung tumor specimens from AA and EA. Pathway enrichment, predicted drug response, tumor microenvironment infiltration, cancer immunotherapy antigen profiling, and microRNA target enrichment were assessed. Results: AA-enriched differential gene expression was characterized by stem-cell and invasion pathways. Differential gene expression in lung tumors from EA were primarily characterized by cell proliferation pathways. Population-specific gene expression was partly driven by population-specific miRNA expression profiles. Drug susceptibility predictions revealed a strong inverse correlation between AA resistance and EA sensitivity to the same panel of drugs. Statistically significant differences in M1 and M2 macrophage infiltration was observed in AA (P <0.05), however, PD-L1, PD-L2 expression was similar between both. Conclusions: Comparative transcriptomic profiling revealed clear differences in lung tumor biology between AA and EA. Increased participation by AA in lung cancer clinical trials are needed to integrate, and leverage, transcriptomic differences with other clinical information to maximize therapeutic benefit in both AA and EA.

Dataset Information

Investigation of the locus near MC4R with childhood obesity in Americans of European and African ancestry.

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Investigation of the locus near MC4R with childhood obesity in Americans of European and African ancestry.

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