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Human metabolic individuality in biomedical and pharmaceutical research.

ABSTRACT: Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci associated with blood metabolite concentrations, of which 25 show effect sizes that are unusually high for GWAS and account for 10-60% differences in metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including those for cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn's disease. The study advances our knowledge of the genetic basis of metabolic individuality in humans and generates many new hypotheses for biomedical and pharmaceutical research.

SUBMITTER: Suhre K

PROVIDER: S-EPMC3832838 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Human metabolic individuality in biomedical and pharmaceutical research.

Suhre Karsten K Shin So-Youn SY Petersen Ann-Kristin AK Mohney Robert P RP Meredith David D Wägele Brigitte B Altmaier Elisabeth E Deloukas Panos P Erdmann Jeanette J Grundberg Elin E Hammond Christopher J CJ de Angelis Martin Hrabé MH Kastenmüller Gabi G Köttgen Anna A Kronenberg Florian F Mangino Massimo M Meisinger Christa C Meitinger Thomas T Mewes Hans-Werner HW Milburn Michael V MV Prehn Cornelia C Raffler Johannes J Ried Janina S JS Römisch-Margl Werner W Samani Nilesh J NJ Small Kerrin S KS Wichmann H-Erich HE Zhai Guangju G Illig Thomas T Spector Tim D TD Adamski Jerzy J Soranzo Nicole N Gieger Christian C

Nature 20110831 7362

Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci as ...[more]

PMID: 21886157

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Project description:PurposeThe analysis of existing institutional research proposal databases can provide novel insights into science funding parity. The purpose of this study was to analyze the relationship between race/ethnicity and extramural research proposal and award rates across a medical school faculty and to determine whether there was evidence that researchers changed their submission strategies because of differential inequities across submission categories.MethodThe authors performed an analysis of 14,263 biomedical research proposals with proposed start dates between 2010-2022 from the University of Michigan Medical School, measuring the proposal submission and award rates for each racial/ethnic group across 4 possible submission categories (R01 & Equivalent programs, other federal, industry, and non-profit).ResultsResearchers from each self-identified racial/ethnic group (Asian, Black/African American, Hispanic/Latino) pursued a different proposal submission strategy than the majority group (White). The authors found that Black/African American researchers experienced negative award rate differentials across all submission categories, which resulted in the lowest R01 & Equivalent and Other Federal submission rates of any racial/ethnic group and the highest submission rate to non-profit sources. The authors did not find support for the hypothesis that researchers changed submission strategies in response to award rate inequalities across submission categories.ConclusionsBiomedical researchers from different racial/ethnic groups follow markedly different proposal submission strategies within the University of Michigan Medical School. There is also a clear relationship between race/ethnicity and rates of proposal award. Black/African American and Asian researchers appear disadvantaged across all submission categories relative to White researchers. This study can be easily replicated by other academic research institutions, revealing opportunities for positive intervention.

Dataset Information

Human metabolic individuality in biomedical and pharmaceutical research.

Publications

Human metabolic individuality in biomedical and pharmaceutical research.

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