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- Title
Identification of new schizophrenia susceptibility loci in an ethnically homogeneous, family-based, Arab-Israeli sample.
- Authors
Alkelai, Anna; Lupoli, Sara; Greenbaum, Lior; Giegling, Ina; Kohn, Yoav; Sarner-Kanyas, Kyra; Ben-Asher, Edna; Lancet, Doron; Rujescu, Dan; Macciardi, Fabio; Lerer, Bernard
- 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=1.22x10-11) 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 die 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.
- Subjects
GENOMES; SAMPLING (Process); GENETICS of schizophrenia; LOCUS (Genetics); CHROMOSOMES; GENETIC polymorphisms; TRANSCRIPTION factors
- Publication
FASEB Journal, 2011, Vol 25, Issue 11, p4011
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.11-184937