A genome-wide autosomal screen for schizophrenia susceptibility loci in 71 families with affected siblings: support for loci on chromosome 10p and 6

S.G. Schwab, J. Hallmayer, M. Albus, B. Lerer, G.N. Eckstein, M. Borrmann, R.H. Segman, C.A. Hanses, J. Freymann, A. Yakir, M. Trixler, P. Falkai, M. Rietschel, W. Maier, D.B. Wildenauer

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    144 Citations (Scopus)

    Abstract

    Evidence from epidemiological studies and segregation analysis suggests oligo- or polygenic inheritance in schizophrenia. Since model independent methods are thought to be most appropriate for linkage analysis in complex disorders, we performed a genome-wide autosomal screen in 71 families from Germany and Israel containing 86 independent affected sib-pairs with parental genotype information for statistical analysis strictly identity by descent, We genotyped 305 individuals with 463 markers at an average distance of approximately 10 cM genome-wide, and 1-2 cM in candidate regions (5q, 6p, q, 8p, 10p, 18p, 22q). The highest multipoint LOD scores (ASPEX) were obtained on 6p (D6S260, LOD = 2.0; D6S274, LOD = 2.2, MHC region, LOD = 2.15) and on 10p (D10S1714, LOD = 2.1), followed by 5q (D5S2066, LOD = 1.36), 6q (D6S271, LOD = 1.12; D6S1613, LOD = 1.11), Iq (D1S2675, LOD = 1.04), and 18p (broad disease model: D18S1116, LOD = 1.0), One hundred and thirty-three additional family members were available for some of the families (extended families) and were genotyped for these regions. GENEHUNTER produced a maximum NPL of 3.3 (P = 0.001) for the MHC region and NPL of 3.13 (P = 0.0015) for the region on 10p, There is support for these regions by independent groups. In genome-wide TDT analysis (sTDT, implemented in ASPEX), no marker passed the significance level of 0.0001 given by multiple testing, but nominal significance values for D10S211 (P = 0.03) and for GOLF (P = 0.0032) support further the linkage results on 10p and 18p, Our survey of 22 chromosomes identified candidate regions which should be useful to screen for schizophrenia susceptibility genes.
    Original languageEnglish
    Pages (from-to)638-649
    JournalMolecular Psychiatry
    Volume5
    DOIs
    Publication statusPublished - 2000

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