Data di Pubblicazione:
2012
Citazione:
DOCK4 and CEACAM21 as novel schizophrenia candidate genes in the Jewish population / A. Alkelai, S. Lupoli, L. Greenbaum, Y. Kohn, K. Kanyas-Sarner, E. Ben-Asher, D. Lancet, F. Macciardi, B. Lerer. - In: INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY. - ISSN 1461-1457. - 15:4(2012), pp. 459-469.
Abstract:
It is well accepted that schizophrenia has a strong genetic component.
Several genome-wide association studies (GWASs) of schizophrenia have
been published in recent years; most of them population based with a
case-control design. Nevertheless, identifying the specific genetic
variants which contribute to susceptibility to the disorder remains a
challenging task. A family-based GWAS strategy may be helpful in the
identification of schizophrenia susceptibility genes since it is
protected against population stratification, enables better accounting
for genotyping errors and is more sensitive for identification of rare
variants which have a very low frequency in the general population. In
this project we implemented a family-based GWAS of schizophrenia in a
sample of 107 Jewish-Israeli families. We found one genome-wide
significant association in the intron of the DOCK4 gene (rs2074127, p
value=1.134 x 10(-7)) and six additional nominally significant
association signals with p<1 x 10(-5). One of the top single nucleotide
polymorphisms (p<1 x 10(-5)) which is located in the predicted intron of
the CEACAM21 gene was significantly replicated in independent
family-based sample of Arab-Israeli origin (rs4803480: p value=0.002;
combined p value=9.61 x 10(-8)), surviving correction for multiple
testing. Both DOCK4 and CEACAM21 are biologically reasonable candidate
genes for schizophrenia although generalizability of the association of
DOCK4 with schizophrenia should be investigated in further studies. In
addition, gene-wide significant associations were found within three
schizophrenia candidate genes: PGBD1, RELN and PRODH, replicating
previously reported associations. By application of a family-based
strategy to GWAS, our study revealed new schizophrenia susceptibility
loci in the Jewish-Israeli population.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
CEACAM21; DOCK4; genes; GWAS; schizophrenia
Elenco autori:
A. Alkelai, S. Lupoli, L. Greenbaum, Y. Kohn, K. Kanyas-Sarner, E. Ben-Asher, D. Lancet, F. Macciardi, B. Lerer
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