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Consangunity and psychosis in Algeria. A family study

Published online by Cambridge University Press:  15 April 2020

A. Dahdouh Guermouche*
Affiliation:
Departement of psychiatry, university hospital of Oran, Oran, Algeria
J. Prados
Affiliation:
Departement of medical genetics, university hospital of Geneva, Geneva, Switzerland
M. Guipponi
Affiliation:
Departement of medical genetics, university hospital of Geneva, Geneva, Switzerland
F. Bena
Affiliation:
Departement of medical genetics, university hospital of Geneva, Geneva, Switzerland
L. Stenz
Affiliation:
Departement of medical genetics, university hospital of Geneva, Geneva, Switzerland
B. Semaoune
Affiliation:
Departement of psychiatry, Central army hospitalAlgeria
S. Antonarakis
Affiliation:
Departement of medical genetics, university hospital of Geneva, Geneva, Switzerland
H. Hamamy
Affiliation:
Departement of medical genetics, university hospital of Geneva, Geneva, Switzerland
*
*Adresse e-mail[email protected]

Abstract

Several studies have affirmed the existence of a strong and complex genetic component in the determination of psychotic disorders. However, the genetic architecture of these disorders remains poorly understood. GWAS studies conducted over the past decade have identified some associations to low effect, and the major part of this heritability remains unexplained, thus calling into question the hypothesis of “common disease – common variant” for model involving a large number of rare variants. Family studies of extended pedigrees selected from geographical isolate can be a powerful approach in identifying rare genetic variants of complex diseases such as psychotic disorders. Here, we studied four multigenerational families in which co-exist psychotic and mood disorders and a high rate of consanguinity, identified in the northwest of Algeria. This case-control study aimed to characterize new rare genetic variants responsible for psychosis. These families have received complete clinical and genealogical investigations, genome wide analysis that were performed in the laboratory of medical genetics in the university hospital of Geneva. A genome wide research CNVs using Agilent Human Genome CGH Microarray Kit 44 K, covering 45 subjects including 20 patients and in a control population of 55 individuals. Three CNVs that had never been reported to date have been identified in one of four families and validated by two techniques. It is the dup 4q26, and 16q23.1 del del21q21. These CNVs are transmitted by either parent line, suggesting a cumulative effect on the risk of psychotic disorders. Further analyzes using pan-genomic linkage analysis using GWAS chip (Illumina Human 660 W-Quad v1.0 Breadchip) and complete WES (by GAIIx Illumina/HiSeq 2000) were performed in some related individuals to search other mutations may explain the appearance of the phenotype in this population.

Type
Congrès français de psychiatrie: Rencontres avec l’expert
Copyright
Copyright © European Psychiatric Association 2015

Disclosure of interest

The authors declare that they have no competing interest.

References

Further reading

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