Evidence for the multigenic inheritance of schizophrenia

Citation
R. Freedman et al., Evidence for the multigenic inheritance of schizophrenia, AM J MED G, 105(8), 2001, pp. 794-800
Citations number
50
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
AMERICAN JOURNAL OF MEDICAL GENETICS
ISSN journal
0148-7299 → ACNP
Volume
105
Issue
8
Year of publication
2001
Pages
794 - 800
Database
ISI
SICI code
0148-7299(200112)105:8<794:EFTMIO>2.0.ZU;2-M
Abstract
Schizophrenia is assumed to have complex inheritance because of its high pr evalence and sporadic familial transmission. Findings of linkage on differe nt chromosomes in various studies corroborate this assumption. It is not kn own whether these findings represent heterogeneous inheritance, in which va rious ethnic groups inherit illness through different major gene effects, o r multigenic inheritance, in which affected individuals inherit several com mon genetic abnormalities. This study therefore examined inheritance of sch izophrenia at different genetic loci in a nationally collected European Ame rican and African American sample. Seventy-seven families were previously g enotyped at 458 markers for the NIMH Schizophrenia Genetics Initiative. Ini tial genetic analysis tested a dominant model, with schizophrenia and schiz oaffective disorder, depressed type, as the affected phenotype. The familie s showed one genome-wide significant linkage (Z = 3.97) at chromosome 15q14 , which maps within 1 cM of a previous linkage at the alpha7-nicotinic rece ptor gene. Chromosome 10p13 showed suggestive linkage (Z = 2.40). Six other s (6q21, 9q32, 13q32, 15q24, 17p12, 20q13) were positive, with few differen ces between the two ethnic groups. The probability of each family transmitt ing schizophrenia through two genes is greater than expected from the combi nation of the independent segregation of each gene. Two trait-locus linkage analysis supports a model in which genetic alleles associated with schizop hrenia are relatively common in the general population and affected individ uals inherit risk for illness through at least two different loci. (C) 2001 Wiley-Liss, Inc.