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. 2001 Mar;68(3):661-73.
doi: 10.1086/318788.

Genomewide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q32.2, 5q33.2, and 8p21-22 and provides support for linkage to schizophrenia, on chromosomes 11q23.3-24 and 20q12.1-11.23

H M Gurling  1 , G Kalsi, J Brynjolfson, T Sigmundsson, R Sherrington, B S Mankoo, T Read, P Murphy, E Blaveri, A McQuillin, H Petursson, D Curtis
Affiliations

Genomewide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q32.2, 5q33.2, and 8p21-22 and provides support for linkage to schizophrenia, on chromosomes 11q23.3-24 and 20q12.1-11.23

H M Gurling et al. Am J Hum Genet. 2001 Mar.

Abstract

We have performed genetic linkage analysis in 13 large multiply affected families, to test the hypothesis that there is extensive heterogeneity of linkage for genetic subtypes of schizophrenia. Our strategy consisted of selecting 13 kindreds containing multiple affected cases in three or more generations, an absence of bipolar affective disorder, and a single progenitor source of schizophrenia with unilineal transmission into the branch of the kindred sampled. DNA samples from these families were genotyped with 365 microsatellite markers spaced at approximately 10-cM intervals across the whole genome. We observed LOD scores >3.0 at five distinct loci, either in the sample as a whole or within single families, strongly suggesting etiological heterogeneity. Heterogeneity LOD scores >3.0 in the sample as a whole were found at 1q33.2 (LOD score 3.2; P=.0003), 5q33.2 (LOD score 3.6; P=.0001), 8p22.1-22 (LOD score 3.6; P=.0001), and 11q21 (LOD score 3.1; P=.0004). LOD scores >3.0 within single pedigrees were found at 4q13-31 (LOD score 3.2; P=.0003) and at 11q23.3-24 (LOD score 3.2; P=.0003). A LOD score of 2.9 was also found at 20q12.1-11.23 within in a single family. The fact that other studies have also detected LOD scores >3.0 at 1q33.2, 5q33.2, 8p21-22 and 11q21 suggests that these regions do indeed harbor schizophrenia-susceptibility loci. We believe that the weight of evidence for linkage to the chromosome 1q22, 5q33.2, and 8p21-22 loci is now sufficient to justify intensive investigation of these regions by methods based on linkage disequilibrium. Such studies will soon allow the identification of mutations having a direct effect on susceptibility to schizophrenia.

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Figures

Figure 1
Figure 1
Graphs of three-point LOD scores for schizophrenia against map position (cM), for MALODs with different definitions of affection and for HLODs, under assumptions of dominant and recessive transmission. Blackened diamonds (⧫) = MALOD, core affection model; unblackened squares (□) = MALOD, combined (core and spectrum) affection model; solid line (——) = HLOD, combined (core and spectrum) affection model, dominant transmission; dashed line (- - - -) = HLOD, combined (core and spectrum) affection model, recessive transmission.
Figure 1
Figure 1
Graphs of three-point LOD scores for schizophrenia against map position (cM), for MALODs with different definitions of affection and for HLODs, under assumptions of dominant and recessive transmission. Blackened diamonds (⧫) = MALOD, core affection model; unblackened squares (□) = MALOD, combined (core and spectrum) affection model; solid line (——) = HLOD, combined (core and spectrum) affection model, dominant transmission; dashed line (- - - -) = HLOD, combined (core and spectrum) affection model, recessive transmission.
See this image and copyright information in PMC

References

Electronic-Database Information

    1. MFLINK Documentation, http://www.hgmp.mrc.ac.uk/Registered/Help/mflink/ (for MFLINK documentation and software-downloading information)
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for SCZD [MIM 181500], SCZD1 C5p [MIM 181510], SCZD2 C11q24 [MIM 603342], SCZD3 C6p22-24 [MIM 600511], SCZD4 22q12-Q13.1.2 [MIM 600850], SCZD5 C6q21 [MIM 603175], SCZD6 C8p21-22 [MIM 603013], and SCZD9 C1q21-22 [MIM 604906])
    1. Results of genome scan for schizophrenia, http://www.mds.qmw.ac.uk/statgen/dcurtis/szscan.html (Tables of all two-point admixture LOD scores, three-point admixture LOD scores, HLOD scores under dominant and recessive transmission, and MFLINK LOD scores (MLOD, MALOD, MFLOD) for schizophrenia under the core and spectrum models)

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