Identification of new schizophrenia susceptibility loci in an ethnically homogeneous, family-based, Arab-Israeli sample
Articolo
Data di Pubblicazione:
2011
Citazione:
Identification of new schizophrenia susceptibility loci in an ethnically homogeneous, family-based, Arab-Israeli sample / A. Alkelai, S. Lupoli, L. Greenbaum, I. Giegling, Y. Kohn, K. Sarner-Kanyas, E. Ben-Asher, D. Lancet, D. Rujescu, F. Macciardi, B. Lerer. - In: THE FASEB JOURNAL. - ISSN 0892-6638. - 25:11(2011 Nov), pp. 4011-4023.
Abstract:
While the use of population-based samples is a common strategy in genome-wide association studies (GWASs), family-based samples have considerable advantages, such as robustness against population stratification and false-positive associations, better quality control, and the possibility to check for both linkage and association. In a genome-wide linkage study of schizophrenia in Arab-Israeli families with multiple affected individuals, we previously reported significant evidence for a susceptibility locus at chromosome 6q23.2-q24.1 and suggestive evidence at chromosomes 10q22.3-26.3, 2q36.1-37.3 and 7p21.1-22.3. To identify schizophrenia susceptibility genes, we applied a family-based GWAS strategy in an enlarged, ethnically homogeneous, Arab-Israeli family sample. We performed genome-wide single nucleotide polymorphism (SNP) genotyping and single SNP transmission disequilibrium test association analysis and found genome-wide significant association (best value of P=1.22×10(-11)) for 8 SNPs within or near highly reasonable functional candidate genes for schizophrenia. Of particular interest are a group of SNPs within and flanking the transcriptional factor LRRFIP1 gene. To determine replicability of the significant associations beyond the Arab-Israeli population, we studied the association of the significant SNPs in a German case-control validation sample and found replication of associations near the UGT1 subfamily and EFHD1 genes. Applying an exploratory homozygosity mapping approach as a complementary strategy to identify schizophrenia susceptibility genes in our Arab Israeli sample, we identified 8 putative disease loci. Overall, this GWAS, which emphasizes the important contribution of family based studies, identifies promising candidate genes for schizophrenia.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Genetic Linkage ; Polymorphism, Single Nucleotide ; Humans ; Chromosomes, Human, Pair 6 ; Genome-Wide Association Study ; Schizophrenia ; Chromosomes, Human, Pair 2 ; European Continental Ancestry Group ; RNA-Binding Proteins ; Arabs; Case-Control Studies ; Genetic Predisposition to Disease ; Family Health
Elenco autori:
A. Alkelai, S. Lupoli, L. Greenbaum, I. Giegling, Y. Kohn, K. Sarner-Kanyas, E. Ben-Asher, D. Lancet, D. Rujescu, F. Macciardi, B. Lerer
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