Approved Research
Analysis of potential pleiotropic effects of specific target genes of interest, through a comprehensive PheWAS analysis across a large population.
Lay summary
Complex diseases, which are caused by the interaction of multiple genes, such as asthma, type 2 diabetes, or some skin disorders have been broadly studied at the genomic level during the last decades. As a result, thousands of genomic variants have been found associated with these diseases, thus enhancing their detection, prevention, and treatment. However, there are still many genomic studies that can be done to complement and improve the genetic knowledge of complex diseases. In this direction, we have developed new methods which can enhance the study of the effect of genomic variants in multiple traits or diseases, which is also named pleiotropy.
The common way to study pleiotropy is to test if a variant is simultaneously associated with two or more related traits. Therefore, to find pleiotropic variants it is necessary to perform an association test with diverse phenotypes. To do this type of analysis, we have currently developed and published a method, which facilitates the inclusion and, therefore, the genotype-phenotype test of more good quality genomic variants. Therefore, although some large-scale initiatives have already globally inspected pleiotropy based on previously published association studies results, there are still some variants which have been completely disregarded or even excluded from the analyses.
To find pleiotropic variants associated with some skin disorders, we will focus on a reduced set of variants with a certain known relation with genes linked with the disease. Then, we will use the UK Biobank cohort to test the association between these variants and diverse traits and complex diseases. As a result, we will obtain a list of variants associated with multiple traits or diseases.
Given the complexity of the project, its estimated duration is of 3 years. The outcomes of these analyses are expected to provide a better understanding of the pathophysiology of complex diseases, to result in high impact scientific publications, and to ultimately help diagnose and treat complex diseases in a personalised manner. Particularly, being in a collaboration with a pharmaceutical company, Almirall, these outcomes will be evaluated for the generation of drug discovery programs and, therefore, to produce new and/or more effective therapies for skin diseases.