Inserm-University Paris Diderot UMR 946 – Genetic Variation and Human Diseases

Director : Florence Demenais

The main objectives of the research program of UMR-946 (Inserm-University Paris Diderot) are :

  • to identify the genetic factors involved in human diseases
  • to understand their mode of action
  • to characterize the other factors (environment, life style..) which may modulate the effect of genes on disease.

This program is organized around two complementary themes:

  1. Statistical Methodology in Genetic Epidemiology.
  2. Genetic Epidemiology of Multifactorial Diseases.

These two themes are complementary since statistical methods can define the optimal study designs and analysis strategies for the identification of the genetic and environmental determinants of human diseases and the genetic epidemiology studies of these diseases can raise specific issues to which methodological development can respond.

1. Statistical Methodology in Genetic Epidemiology

The aims of our methodological developments are:

  • to address complex mechanisms underlying common multifactorial diseases such as gene-gene, gene-environment interactions, pleiotropy, genetic heterogeneity
    to extend methods based on consanguinity and population genetics to facilitate gene identification
  • to allow examination of a broad spectrum of genetic variation from rare to common genetic variants.
  • to allow integration of multiple levels of “omics” data (genomics, transcriptomics, epigenomics,…)

2. Genetic Epidemiology of Multifactorial Diseases

Our genetic epidemiology studies focus mainly on asthma and allergic diseases and cancers. These studies rest on large data collections we have been gathering for various cancers (melanoma, lung and head and neck cancers, bladder cancer) or to which our unit is tightly associated (the Epidemiological study on the Genetics and Environment of Asthma (EGEA). These studies integrate genome-wide association studies and large scale biology approaches applied to many well characterized disease-related phenotypes. They are conducted in a multidisciplinary setting and in the framework of many collaborations at the National, European and international levels.

The main objectives of these studies are:

  • to identify new genes and gene-environment interactions involved in disease
  • to better understand the molecular mechanisms underlying disease
  • to contribute to translation of research into medical applications

Altogether, the UMR-946 research program is designed to respond to the new challenges raised by high-throughput genotyping and sequencing technologies and large scale biology approaches in order to progress towards a system biology-based approach of disease.