Complex traits & multi-factorial diseases
The identification of genes underlying complex phenotypes and multifactorial diseases is a challenging task. In spite of an explosion of genome-wide studies, a limited number of confirmed genetic variants influencing human complex diseases have been identified. In addition, their genetic contribution to a given phenotype or disease is very small, and explains only a small proportion of heritability, which is the portion of phenotypic variance explained by genetic factors. It is thought that the unexplained heritability is partly due to gene-gene and gene-environment interactions. Indeed, such interactions have been identified in some multifactorial diseases, such as asthma.
It is expected that genetic variations having either a small effect or no detectable effect individually, act through interactions with environment and/or other genes in most multifactorial diseases. The existence of gene expression profiles associated with multifactorial diseases supports this view. Also, it is very likely that a combination of genetic variants within cis-regulatory regions or epigenetic modifications can deregulate the expression of a number of genes within a molecular network, thus causing the disease.
Malaria, sepsis, and cancers are multifactorial diseases influenced by genetic and environmental factors. Here, we aim at identifying genetic variants and/or deregulated networks associated with the diseases. This will provide new insights into diagnosis and prognosis knowledge, and will allow modelling the pathological systems for malaria, sepsis, and cancers. In the continuity of the previous mandate strategy, we will magnify studies involving immune system and haematological components, and will continue studies in solid tumors as a bridgehead for the development of new high throughput analyses such as large scale epigenetic approaches. Finally, we aim at identifying some common genes and pathways involved in different diseases.