RESUMO
Genome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development and clinical guidelines. However, the majority of discovery efforts are based on data from populations of European ancestry1-3. In light of the differential genetic architecture that is known to exist between populations, bias in representation can exacerbate existing disease and healthcare disparities. Critical variants may be missed if they have a low frequency or are completely absent in European populations, especially as the field shifts its attention towards rare variants, which are more likely to be population-specific4-10. Additionally, effect sizes and their derived risk prediction scores derived in one population may not accurately extrapolate to other populations11,12. Here we demonstrate the value of diverse, multi-ethnic participants in large-scale genomic studies. The Population Architecture using Genomics and Epidemiology (PAGE) study conducted a GWAS of 26 clinical and behavioural phenotypes in 49,839 non-European individuals. Using strategies tailored for analysis of multi-ethnic and admixed populations, we describe a framework for analysing diverse populations, identify 27 novel loci and 38 secondary signals at known loci, as well as replicate 1,444 GWAS catalogue associations across these traits. Our data show evidence of effect-size heterogeneity across ancestries for published GWAS associations, substantial benefits for fine-mapping using diverse cohorts and insights into clinical implications. In the United States-where minority populations have a disproportionately higher burden of chronic conditions13-the lack of representation of diverse populations in genetic research will result in inequitable access to precision medicine for those with the highest burden of disease. We strongly advocate for continued, large genome-wide efforts in diverse populations to maximize genetic discovery and reduce health disparities.
Assuntos
Povo Asiático/genética , População Negra/genética , Estudo de Associação Genômica Ampla/métodos , Hispânico ou Latino/genética , Grupos Minoritários , Herança Multifatorial/genética , Saúde da Mulher , Estatura/genética , Estudos de Coortes , Feminino , Genética Médica/métodos , Equidade em Saúde/tendências , Disparidades nos Níveis de Saúde , Humanos , Masculino , Estados UnidosRESUMO
Data analysis processes in scientific applications can be expressed as coarse-grain workflows of complex data processing operations with data flow dependencies between them. Performance optimization of these workflows can be viewed as a search for a set of optimal values in a multidimensional parameter space consisting of input performance parameters to the applications that are known to affect their execution times. While some performance parameters such as grouping of workflow components and their mapping to machines do not affect the accuracy of the analysis, others may dictate trading the output quality of individual components (and of the whole workflow) for performance. This paper describes an integrated framework which is capable of supporting performance optimizations along multiple such parameters. Using two real-world applications in the spatial, multidimensional data analysis domain, we present an experimental evaluation of the proposed framework.
RESUMO
Data analysis processes in scientific applications can be expressed as coarse-grain workflows of complex data processing operations with data flow dependencies between them. Performance optimization of these workflows can be viewed as a search for a set of optimal values in a multi-dimensional parameter space. While some performance parameters such as grouping of workflow components and their mapping to machines do not a ect the accuracy of the output, others may dictate trading the output quality of individual components (and of the whole workflow) for performance. This paper describes an integrated framework which is capable of supporting performance optimizations along multiple dimensions of the parameter space. Using two real-world applications in the spatial data analysis domain, we present an experimental evaluation of the proposed framework.