Evidence for an interaction of schizophrenia susceptibility loci on chromosome 6q23.3 and 10q24.33-q26.13 in Arab Israeli families

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Vol. 150B; no. 7; pp. 914 - 925
• Main Authors: Alkelai, A., Kohn, Y., Olender, T., Sarner-Kanyas, K., Rigbi, A., Hamdan, A., Ben-Asher, E., Lancet, D., Lerer, B.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 05-10-2009; Wiley-Liss
• Subjects: Adult and adolescent clinical studies; Arabs - genetics; Asian Continental Ancestry Group - genetics; Biological and medical sciences; chromosome 10q; chromosome 6q; Chromosomes, Human, Pair 10 - genetics; Chromosomes, Human, Pair 6 - genetics; Classical genetics, quantitative genetics, hybrids; epistasis; Epistasis, Genetic; Family; Fundamental and applied biological sciences. Psychology; Genetic Linkage; Genetic Predisposition to Disease; Genetics of eukaryotes. Biological and molecular evolution; Haplotypes; Human; Humans; Israel; Medical genetics; Medical sciences; Microsatellite Repeats - genetics; Models, Genetic; Penetrance; Physical Chromosome Mapping; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Quantitative Trait Loci - genetics; Schizophrenia; Schizophrenia - genetics; two locus linkage; Israel; Genetic mapping; chromosome 10q;chromosome 6q; Family study; Pathogenesis; Interaction; Schizophrenia; Epistasis; Chromosome C6; two locus linkage; Genetic determinism; Psychosis; Genetic linkage; Predisposition; Genetics; Locus
• ISSN: 1552-4841; 1552-485X
• DOI: 10.1002/ajmg.b.30918

A genome scan for schizophrenia related loci in Arab Israeli families by Lerer et al. [Lerer et al. (2003); Mol Psychiatry 8:488–498] detected significant evidence for linkage at chromosome 6q23. Subsequent fine mapping [Levi et al. (2005); Eur J Hum Genet 13:763–771], association [Amann‐Zalcenstein et al. (2006); Eur J Hum Genet 14:1111–1119] and replication studies [Ingason et al. (2007); Eur J Hum Genet 15:988–991] identified AHI1 as a putative susceptibility gene. The same genome scan revealed suggestive evidence for a schizophrenia susceptibility locus in the 10q23–26 region. Genes at these two loci may act independently in the pathogenesis of the disease in our homogeneous sample of Arab Israeli families or may interact with each other and with other factors in a common biological pathway. The purpose of our current study was to test the hypothesis of genetic interaction between these two loci and to identify the type of interaction between them. The initial stage of our study focused on the 10q23–q26 region which has not been explored further in our sample. The second stage of the study included a test for possible genetic interaction between the 6q23.3 locus and the refined 10q24.33–q26.13 locus. A final candidate region of 19.9 Mb between markers D10S222 (105.3 Mb) and D10S587 (125.2 Mb) was found on chromosome 10 by non‐parametric and parametric linkage analyses. These linkage findings are consistent with previous reports in the same chromosomal region. Two‐locus multipoint linkage analysis under three complex disease inheritance models (heterogeneity, multiplicative, and additive models) yielded a best maximum LOD score of 7.45 under the multiplicative model suggesting overlapping function of the 6q23.3 and 10q24.33–q26.13 loci. © 2009 Wiley‐Liss, Inc.