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

墨西哥生物银行项目：混合人群医学基因组学大数据科学能力建设

• 批准号: MR/N028937/1
• 负责人: Adrian Hill
• 金额: $ 64.65万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FN028937%2F1
• 关键词: Mexican; Biobank; Project; Building; Capacity

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.

技术创新是一个国家经济增长的主要动力。不幸的是，如此迅速的进步往往超出了社会吸收和转化为适用利益的能力。在dna技术爆炸式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，为了让这些进步使新兴经济体受益，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——减少发达国家和发展中国家之间存在的科学差距。这种学术发展可以通过国际合作研究来促进。我们建议对迄今为止墨西哥人口中最全面的DNA生物库进行遗传分析。通过这样做，我们将建设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以及将其转化为改善卫生保健。遗传图谱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和解决特定人群健康问题的有力工具。英国生物银行（UK Biobank）和法罗基因组计划（Faroe Genome Project）等全国性的举措，试图实现一个由人口基因组成指导医疗保健的未来。然而，大多数旨在阐明健康与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像墨西哥这样的混合人口。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，这些数据将使开展包括全基因组关联研究（GWAS）在内的一系列遗传研究成为可能。作为概念验证，我们将首先专注于重复识别已知与调查队列中存在的免疫和代谢综合征相关的变异。具体来说，我们将测量对一系列病原体的抗体反应，其中许多病原体在墨西哥人群中广泛流行，并且已经认识到与人类基因组中人类白细胞抗原位点的变异有关。我们还将重新测试ENSA生物库中可用的与心脏代谢特征的遗传关联（例如血糖和体重指数）。通过在参与ENSA 2000的大多数个体中使用多种表型进行遗传关联研究，我们将能够概括其他大型倡议（如UK Biobank）使用的方法。我们的研究不仅可以很好地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口独特的混合结构来详细描述这些关联。这个项目将通过发展本国的研究能力，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建立一个基础，将伦理获取、储存、基因分型、测序和分析都纳入墨西哥等发展中国家的独立研究。我们预见，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，改善一般人口的医疗保健。我们的愿望是建立一个路线图，进一步促进其他人口类似混合的发展中经济体的自主权，并确保这些技术进步真正成为全球性的。

项目成果

A loss-of-function IFNAR1 allele in Polynesia underlies severe viral diseases in homozygotes.

• DOI: 10.1084/jem.20220028
• 发表时间: 2022-06-06
• 期刊: The Journal of experimental medicine

The Human Leukocyte Antigen Locus and Rheumatic Heart Disease Susceptibility in South Asians and Europeans

• DOI: 10.1038/s41598-020-65855-8
• 发表时间: 2020-06-02
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Auckland, Kathryn;Mittal, Balraj;Parks, Tom
• 通讯作者: Parks, Tom

Native American gene flow into Polynesia predating Easter Island settlement.

• DOI: 10.1038/s41586-020-2487-2
• 发表时间: 2020-07
• 期刊: Nature
• 影响因子: 64.8
• 作者: Ioannidis AG;Blanco-Portillo J;Sandoval K;Hagelberg E;Miquel-Poblete JF;Moreno-Mayar JV;Rodríguez-Rodríguez JE;Quinto-Cortés CD;Auckland K;Parks T;Robson K;Hill AVS;Avila-Arcos MC;Sockell A;Homburger JR;Wojcik GL;Barnes KC;Herrera L;Berríos S;Acuña M;Llop E;Eng C;Huntsman S;Burchard EG;Gignoux CR;Cifuentes L;Verdugo RA;Moraga M;Mentzer AJ;Bustamante CD;Moreno-Estrada A
• 通讯作者: Moreno-Estrada A

Paths and timings of the peopling of Polynesia inferred from genomic networks.

• DOI: 10.1038/s41586-021-03902-8
• 发表时间: 2021-09
• 期刊: Nature
• 影响因子: 64.8

Imputation Performance in Latin American Populations: Improving Rare Variants Representation With the Inclusion of Native American Genomes.

• DOI: 10.3389/fgene.2021.719791
• 发表时间: 2021
• 期刊: Frontiers in genetics
• 影响因子: 3.7
• 作者: Jiménez-Kaufmann A;Chong AY;Cortés A;Quinto-Cortés CD;Fernandez-Valverde SL;Ferreyra-Reyes L;Cruz-Hervert LP;Medina-Muñoz SG;Sohail M;Palma-Martinez MJ;Delgado-Sánchez G;Mongua-Rodríguez N;Mentzer AJ;Hill AVS;Moreno-Macías H;Huerta-Chagoya A;Aguilar-Salinas CA;Torres M;Kim HL;Kalsi N;Schuster SC;Tusié-Luna T;Del-Vecchyo DO;García-García L;Moreno-Estrada A
• 通讯作者: Moreno-Estrada A