The Mexican Biobank Project: Building Capacity for Big Data Science in Medical Genomics in Admixed Populations

技术创新是一个国家经济增长的主要动力。不幸的是，这种迅速的进步往往超出了社会吸收和转化为实际利益的能力。在DNA技术爆炸性增长和大数据革命到来的推动下，基因组科学处于这一创新的前沿。然而，为了让这些进步惠及新兴经济体，它们的学术界必须发展大基因组数据生成和分析的专业知识--缩小发达国家和发展中国家之间存在的科学差距。我们建议对迄今为止墨西哥人口最全面的DNA生物库进行基因分析。通过这样做，我们将建立墨西哥开展和领导大规模基因组项目的能力，包括本地数据生成，人力资源培训，吸引尖端科学领域的顶级科学家，并将其转化为医疗保健的改善。遗传分析和深度表型分析是帮助更好地了解与疾病相关的个体变异并解决特定人群健康问题的强大工具。英国生物银行和法罗群岛基因组计划等全国性举措，旨在实现未来的医疗保健由其人口的基因组成指导。然而，大多数旨在阐明健康和遗传变异之间关系的研究和方法主要是在欧洲人群中进行的，因此可能不容易适用于混合人口，如墨西哥。为了建立最具包容性的拉丁美洲人口基因组库，我们建议筛选最大的全国性墨西哥生物库，其中包括2000年作为Encuesta Nacional de Salud（ENSA）的一部分收集的40，000个DNA样本。这些样本中的每一个都有相关的临床，经济，社会学和流行病学数据，这将使一系列的遗传研究，包括全基因组关联研究（GWAS）的承诺。作为一个概念的证明，我们将首先专注于复制识别已知与免疫和代谢综合征在调查队列中存在的变异。具体来说，我们将测量抗体对一系列病原体的反应，其中许多病原体在墨西哥人群中广泛流行，并已确认与人类基因组的人类白细胞抗原基因座中的变异相关。我们还将重新测试ENSA生物库中可用的心脏代谢特征（例如血糖和体重指数）的遗传关联。通过使用参与ENSA 2000的大多数个体中测量的多种表型进行遗传关联研究，我们将能够概括其他大规模倡议（如英国生物银行）所使用的方法。我们的研究不仅能够复制在高加索人群中发现的这些信号，而且我们将能够利用墨西哥人群独特的混合结构来详细描述这些关联。 该项目将通过发展本国研究能力，帮助巩固墨西哥正在萌芽的基因组主权。我们的最终目标是为未来的基因组研究奠定基础，包括道德获取，存储，基因分型，测序和分析，所有这些都在墨西哥等发展中国家内自给自足。我们预计，这些做法将为墨西哥高度专业化的专业人员创造就业机会，并从长远来看，改善普通民众的医疗保健。我们的愿望是建立一个路线图，以促进其他发展中经济体的自主权，类似的混合人口，并确保这种技术进步成为真正的全球性。

Technological innovation is a major driving force of a nation's economic growth. Unfortunately, such rapid advances frequently exceed society's capability of assimilation and translation into applicable benefits. Genomic sciences, propelled by the explosive growth of DNA-based technologies and the advent of the Big Data revolution, are at the forefront of this innovation. However, in order for these advances to benefit emerging economies, their academic communities must develop the expertise for big genomic data generation and analysis - reducing the scientific gap that exists between developed and developing countries.Such academic development can be fostered via international collaborative research. We propose to undertake the genetic profiling of the most comprehensive DNA Biobank available of the Mexican population to date. By doing so, we will build the Mexican capacity for embarking and leading large-scale genomic projects, including local data generation, training of human resources, attraction of top-level scientists in cutting-edge science, and translation into health care improvements. Genetic profiling and deep phenotyping are powerful tools that help better understand individuals' variation associated with disease and tackle population-specific health problems. Nation-wide initiatives such as that of the UK Biobank and the Faroe Genome Project, seek to enable a future in which healthcare is guided by the genetic makeup of its population. However, most studies and methods aimed at elucidating the relationships between health and genetic variation are being undertaken in predominantly European cohorts and thus may not be readily applicable to an admixed population such as that of Mexico. In order to establish the most inclusive genomic repository of a Latin American population, we propose to screen the largest nationwide Mexican Biobank, comprising 40,000 DNA samples collected as part of the Encuesta Nacional de Salud (ENSA) in 2000 [1]. Each of these samples has associated clinical, economic, sociological and epidemiological data that will enable the undertaking of a range of genetic studies including genome wide association studies (GWAS).As a proof of concept, we will first focus on replicating the identification of variants known to be associated with immune and metabolic syndromes present in the surveyed cohort. Specifically, we will measure antibody responses to a range of pathogens, many of which are widely prevalent in the Mexican population and which have recognised associations with variants in the human leukocyte antigen locus of the human genome. We will also re-test genetic associations with cardiometabolic traits that are available in the ENSA Biobank (e.g blood glucose and body-mass index). By undertaking genetic association studies using multiple phenotypes measured in most individuals participating in ENSA 2000 we will be able to recapitulate the approach used by other large-scale initiatives such as UK Biobank. Our study will be particularly well poised to not only replicate these signals discovered in Caucasian populations but we will be able to harness the uniquely admixed structure of the Mexican population to characterize these associations in fine detail. This project will help solidify Mexico's budding genomic sovereignty through the development of endogenous research capacity. Our final aim is to build a foundation for future genomic research incorporating ethical acquisition, storage, genotyping, sequencing and analysis all self-contained within developing countries such as Mexico. We foresee that these practices will create jobs for highly specialized professionals in Mexico and, in the long term, improve healthcare for the general population. Our aspiration is to establish a Roadmap that will further the autonomy of other developing economies with similarly admixed populations and ensure that such technology advances become truly global.