Gemae

GEMAE is the acronym of the R&D project "GEnomics and Metagenomics of Asthma Exacerbations". This project is funded by the grant SAF2017-83417R by the Spanish Ministry of Economy, Industry and Competitiveness, the State Research Agency, and the European Regional Development Funds from the European Union (MINECO/AEI/FEDER, UE) to Maria Pino-Yanes and Fabian Lorenzo-Diaz. This project started in 2018 and it is aimed to understand how genetic variants across the whole human genome and the human microbiome influence in the development of asthma exacerbation.

The main hypothesis of this project is that exacerbations of asthma are caused by a combination of the intrinsic genetic factors of the individual, changes in the respiratory microbiome and the interaction between both factors. Thereby, the objectives of this project are:

Objective 1. To identify human genetic variants associated with the development of asthma exacerbations

Objective 2. To explore changes in the bacterial communities from the oral cavity and the respiratory tract in patients with asthma who develop exacerbations

Objective 3. To analyze the association between human genetic variants and changes in the human microbiome related to the development of asthma exacerbations

The first aim represents the largest genomic study of asthma exacerbations performed to date, including a total of 10,181 individuals from diverse populations with and without exacerbations from different national and international cohorts. Integrative data analysis will be conducted by using different approaches (genomic association study of millions of variants, data integration in biological processes, and admixture mapping), and the results will be validated in another set of 3,886 samples from independent studies.

In the second and third aim, novel aspects will be evaluated in the context of genomics and metagenomics of asthma exacerbations. Spanish adult asthma patients with controlled asthma and with exacerbations at the time of the inclusion will be recruited to create the GEnomics and Metagenomics of Asthma Severity (GEMAS) cohort. In all of them, saliva, nasal and pharyngeal samples will be collected to study the oral cavity and the upper respiratory tract microbiome through next-generation sequencing technologies, and blood samples will be also collected to genotype genetic variants across the genome of these patients. Sequencing of a specific marker will allow to characterize the bacterial diversity and abundance, as well as to infer the functionality of the microbiome in each sample. These parameters will be used to establish correlations between the microbiome and the presence of asthma exacerbations. Finally, the association between the genetic variation and the measurements of abundance, diversity and functions related to exacerbations will be examined.

The results of this study are expected to have a major scientific and socioeconomic impact, contributing to a better understanding of the genetic and molecular mechanisms underlying the development of asthma exacerbations.

GEMAS is the acronym of the cohort GEnomics and Metagenomics of Asthma Severity.  In January 2020, more than 200 patients with asthma have been recruited by the pneumology and allergology departments from different hospitals across Spain. For all of them, saliva samples, nasal, and pharyngeal swabs have been collected to perform an analysis of the human microbiome by means of Next Generation DNA sequencing techniques. Moreover, blood samples have been collected in EDTA tubes and PAXgene tubes to genotype genetic variants across the human genome and to perform gene expression analyses. Adults patients have been recruited in the Canary Islands (Spain) in the General Hospital of La Palma, University Hospital of the Canary Islands and the University Hospital of Nuestra Señora de Candelaria, while children with asthma have been recruited in the Basque Country (Spain) in the University Hospital of Donostia. The recruitment period of this cohort is still open in January 2020.