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Comparative Study
. 2003 Dec;73(6):1355-67.
doi: 10.1086/380206. Epub 2003 Nov 18.

A systematic genomewide linkage study in 353 sib pairs with schizophrenia

N M Williams  1 , N Norton, H Williams, B Ekholm, M L Hamshere, Y Lindblom, K V Chowdari, A G Cardno, S Zammit, L A Jones, K C Murphy, R D Sanders, G McCarthy, M Y Gray, G Jones, P Holmans, V Nimgaonkar, R Adolfson, U Osby, L Terenius, G Sedvall, M C O'Donovan, M J Owen
Affiliations
Comparative Study

A systematic genomewide linkage study in 353 sib pairs with schizophrenia

N M Williams et al. Am J Hum Genet. 2003 Dec.

Abstract

We undertook a genomewide linkage study in a total of 353 affected sib pairs (ASPs) with schizophrenia. Our sample consisted of 179 ASPs from the United Kingdom, 134 from Sweden, and 40 from the United States. We typed 372 microsatellite markers at approximately 10-cM intervals. Our strongest finding was a LOD score of 3.87 on chromosome 10q25.3-q26.3, with positive results being contributed by all three samples and a LOD-1 interval of 15 cM. This finding achieved genomewide significance (P<.05), on the basis of simulation studies. We also found two regions, 17p11.2-q25.1 (maximum LOD score [MLS] = 3.35) and 22q11 (MLS = 2.29), in which the evidence for linkage was highly suggestive. Linkage to all of these regions has been supported by other studies. Moreover, we found strong evidence for linkage (genomewide P<.02) to 17p11.2-q25.1 in a single pedigree with schizophrenia. In our view, the evidence is now sufficiently compelling to undertake detailed mapping studies of these three regions.

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Figures

Figure 1
Figure 1
The results of multipoint ASP linkage analysis of all chromosomes, performed using MAPMAKER/SIBS. LOD scores (left axis) are shown for all ASPs (n=353) in black, and U.K.-only ASPs in red (n=179). Solid and dotted lines refer to narrow and broad diagnostic criteria, respectively. Information content (right axis) at each locus is shown in purple.
Figure 1
Figure 1
The results of multipoint ASP linkage analysis of all chromosomes, performed using MAPMAKER/SIBS. LOD scores (left axis) are shown for all ASPs (n=353) in black, and U.K.-only ASPs in red (n=179). Solid and dotted lines refer to narrow and broad diagnostic criteria, respectively. Information content (right axis) at each locus is shown in purple.
Figure 1
Figure 1
The results of multipoint ASP linkage analysis of all chromosomes, performed using MAPMAKER/SIBS. LOD scores (left axis) are shown for all ASPs (n=353) in black, and U.K.-only ASPs in red (n=179). Solid and dotted lines refer to narrow and broad diagnostic criteria, respectively. Information content (right axis) at each locus is shown in purple.
See this image and copyright information in PMC

References

Electronic-Database Information

    1. Marshfield Center for Medical Genetics, http://www.marshfieldclinic.org/research/genetics/
    1. Online Mendelian Inheritence in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for schizophrenia, 6p24-22, 1q21-22, 13q32-34, 8p21-22, 6q21-25, 22q11-12, SLC6A4, CNP1, ERBB2, CALCYON, GPR10, VCFS, DiGeorge or Shprintzen syndrome, PRODH, COMT, DAAO, NRG1, and DTNBP1)

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