Consanguinité, schizophrénie et trouble bipolaire

Abstract

Consanguinity is a relationship between two people who share a common ancestor. It is usually defined as resulting from sexual reproduction between two related individuals. In other words, consanguineous marriages refer to unions which are contracted between two biologically linked individuals. These unions remain frequent and are widely practiced in certain areas of the globe. The most frequently concerned regions extend from the southern shore of the Mediterranean Sea, across the Middle East, Mesopotamia, the Persian Gulf and sub continental India extending into Southeast Asia. Based on available data, it appears that couples who are second-degree relations or closer and their offspring represent 10.4% of the world's current population. The consequences on the rates of genetically determined diseases are significant, especially in autosomal recessive diseases. Twin and adoption studies as well as risk estimations for the occurrence of mental disorders in families of patients who suffer from mental disorders have confirmed the existence of a genetic component in the vulnerability to numerous psychiatric diseases. Recent techniques examining the entire genome or pan-genomic association studies (Genome-Wide Association Studies or GWAS), have enabled us to identify increasing numbers of genes that are implicated in major mental disorders such as schizophrenia, autism and bipolar disorders. Epidemiological genetic studies in consanguineous populations and/or within geographic isolates have shown an increased rate in infant mortality and morbidity, monogenetic recessive diseases and common multifactorial diseases such as psychotic disorders. These confirm the existence of a significant link between consanguinity, mental disorders and increased risk within the offspring of consanguineous couples. Studies concerning the links between consanguinity and psychotic disorders are few. Rare available data seem to plead in favour of an increased frequency of schizophrenia and bipolar disorder in the offspring of consanguineous parents. The recent discovery of rare genetic variants and their implications in psychotic disorders represents an argument in favour of the " common disease-rare variants" hypothesis. Within this framework, the study of consanguineous families could contribute to testing the links between these rare variants and certain phenotypes and to establish descriptive genotype-phenotype associations. The development of new techniques in molecular genetics should facilitate such studies. All of these aspects show the importance of studying consanguineous populations in order to better understand the role of genetic determinants in psychiatric pathologies and to highlight the interest of genetic counselling in communities with increased risks of mental disorders. This may also enable governments to enact prevention policies and to launch awareness campaigns concerning the risks of consanguineous marriages. © 2013 Elsevier Masson SAS.