Evidence for linkage disequilibrium between the alpha 7-nicotinic receptor gene (CHRNA7) locus and schizophrenia in Azorean families

Recent studies have suggested that the alpha 7‐nicotinic receptor gene (CHRNA7) may play a role in the pathogenesis of schizophrenia. The alpha 7‐nicotinic receptor gene (CHRNA7) is involved in P50 auditory sensory gating deficits, and the genomic locus for this gene lies in the chromosome 15q13–14...

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Published in:American journal of medical genetics 2001-12, Vol.105 (8), p.669-674
Main Authors: Xu, Junzhe, Pato, Michele T., Torre, Camille Dalla, Medeiros, Helena, Carvalho, Celia, Basile, Vincenzo S., Bauer, Amy, Dourado, Ana, Valente, Jose, Soares, Maria Joao, Macedo, Antonio A., Coelho, Isabel, Ferreira, Carlos Paz, Azevedo, M. Helena, Macciardi, Fabio, Kennedy, James L., Pato, Carlos N.
Format: Article
Language:English
Subjects:
Alleles
alpha 7-nicotinic receptor
alpha7 Nicotinic Acetylcholine Receptor
Azores
Azores, Portugal
Biological and medical sciences
DNA - genetics
exon duplication
Family Health
genetic linkage
Genotype
Humans
Linkage Disequilibrium
Medical sciences
Metabolic diseases
Microsatellite Repeats
Obesity
parent-of-origin effect
polymorphism
Portugal
Receptors, Nicotinic - genetics
schizophrenia
Schizophrenia - genetics
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Summary:Recent studies have suggested that the alpha 7‐nicotinic receptor gene (CHRNA7) may play a role in the pathogenesis of schizophrenia. The alpha 7‐nicotinic receptor gene (CHRNA7) is involved in P50 auditory sensory gating deficits, and the genomic locus for this gene lies in the chromosome 15q13–14 regions. The human gene is partially duplicated (exons 5–10) with four novel upstream exons. The marker D15S1360 has been shown to be significantly linked with the phenotype of abnormal P50 suppression in schizophrenia families. The marker L76630 is 3 kb in the 3′ direction from the last exon of the CHRNA7 gene and is located in the duplicated region. The function of the two L76630 copies is unknown. We genotyped three polymorphic markers D15S1360, D15S165, and L76630 that are localized in a genomic fragment containing the CHRNA7 in 31 Azorean schizophrenia families/trios (including 41 schizophrenia individuals and 97 unaffected families members). An overall analysis utilizing the family‐based association test revealed significant linkage disequilibrium between L76630 and schizophrenia (P = 0.0004). Using the extended transmission disequilibrium test and limiting the analysis to one triad per family, transmission disequilibrium of D15S1360 was near significance (P = 0.078). The 15q13 region overlaps with the location of two well‐known genomically imprinted disorders: Angelman syndrome and Prader‐Willi syndrome. Therefore, we investigated maternal and paternal meioses. We found significant transmission disequilibrium for D15S1360 through paternal transmission (P = 0.0006) in our schizophrenia families. The L76630 marker showed a significant disequilibrium in maternal transmissions (P = 0.028). No parent‐of‐origin effect was found in D15S165. Overall, our results suggest that the CHRNA7 may play a role in schizophrenia in these families. A parent of origin effect may be present and requires further study. Published 2001 Wiley‐Liss, Inc.
ISSN:0148-7299
1096-8628
DOI:10.1002/ajmg.1549