Multicenter linkage study of schizophrenia candidate regions on chromosomes 5q, 6q, 10p, and 13q: schizophrenia linkage collaborative group III - PubMed (original) (raw)

Multicenter Study

doi: 10.1086/303041. Epub 2000 Aug 2.

P Holmans, R E Straub, M J Owen, D B Wildenauer, P V Gejman, A E Pulver, C Laurent, K S Kendler, D Walsh, N Norton, N M Williams, S G Schwab, B Lerer, B J Mowry, A R Sanders, S E Antonarakis, J L Blouin, J F DeLeuze, J Mallet

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Multicenter Study

Multicenter linkage study of schizophrenia candidate regions on chromosomes 5q, 6q, 10p, and 13q: schizophrenia linkage collaborative group III

D F Levinson et al. Am J Hum Genet. 2000 Sep.

Abstract

Schizophrenia candidate regions 33-51 cM in length on chromosomes 5q, 6q, 10p, and 13q were investigated for genetic linkage with mapped markers with an average spacing of 5.64 cM. We studied 734 informative multiplex pedigrees (824 independent affected sibling pairs [ASPs], or 1,003 ASPs when all possible pairs are counted), which were collected in eight centers. Cases with diagnoses of schizophrenia or schizoaffective disorder (DSM-IIIR criteria) were considered affected (n=1,937). Data were analyzed with multipoint methods, including nonparametric linkage (NPL), ASP analysis using the possible-triangle method, and logistic-regression analysis of identity-by-descent (IBD) sharing in ASPs with sample as a covariate, in a test for intersample heterogeneity and for linkage with allowance for intersample heterogeneity. The data most supportive for linkage to schizophrenia were from chromosome 6q; logistic-regression analysis of linkage allowing for intersample heterogeneity produced an empirical P value <.0002 with, or P=.0004 without, inclusion of the sample that produced the first positive report in this region; the maximum NPL score in this region was 2.47 (P=.0046), the maximum LOD score (MLS) from ASP analysis was 3.10 (empirical P=.0036), and there was significant evidence for intersample heterogeneity (empirical P=.0038). More-modest support for linkage was observed for chromosome 10p, with logistic-regression analysis of linkage producing an empirical P=. 045 and with significant evidence for intersample heterogeneity (empirical P=.0096).

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Figure 1

Figure 1

For each chromosomal region, maximum LOD score values are shown for each sample and for the combined sample, for multipoint ASP analysis using the possible-triangle method (GENEHUNTER 2.0).

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References

Electronic-Database Information

    1. Marshfield genetic maps, http://www.marshmed.org/genetics/ (for marker locations)
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for review of available evidence for schizophrenia loci [MIM 18150], the chromosome 13q locus studied in this article [as “SCZD7”] [MIM <603176>], and the chromosome 6q locus studied here [as “SCZD5”] [MIM <603175>])
    1. Southampton genetic map, http://cedar.genetics.soton.ac.uk/public_html/ldb.html (for locations of D5S818, D10S1423, and D13S797)

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