title: Identification of new schizophrenia susceptibility loci in an ethnically homogeneous, family-based, Arab-Israeli sample.
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.
authors.affiliation: Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Anna
authors.initials: A
authors.lastname: Alkelai
authors.forename: Sara
authors.initials: S
authors.lastname: Lupoli
authors.forename: Lior
authors.initials: L
authors.lastname: Greenbaum
authors.forename: Ina
authors.initials: I
authors.lastname: Giegling
authors.forename: Yoav
authors.initials: Y
authors.lastname: Kohn
authors.forename: Kyra
authors.initials: K
authors.lastname: Sarner-Kanyas
authors.forename: Edna
authors.initials: E
authors.lastname: Ben-Asher
authors.forename: Doron
authors.initials: D
authors.lastname: Lancet
authors.forename: Dan
authors.initials: D
authors.lastname: Rujescu
authors.forename: Fabio
authors.initials: F
authors.lastname: Macciardi
authors.forename: Bernard
authors.initials: B
authors.lastname: Lerer
mesh_terms: D018912:Arabs / Q000235:genetics; D016022:Case-Control Studies; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D005192:Family Health; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins / Q000235:genetics; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C114370:LRRFIP1 protein, human; D016601:RNA-Binding Proteins