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. 2001 Dec;69(6):1278-89.
doi: 10.1086/324590. Epub 2001 Oct 19.

Genomewide multipoint linkage analysis of seven extended Palauan pedigrees with schizophrenia, by a Markov-chain Monte Carlo method

N J Camp  1 , S L Neuhausen, J Tiobech, A Polloi, H Coon, M Myles-Worsley
Affiliations

Genomewide multipoint linkage analysis of seven extended Palauan pedigrees with schizophrenia, by a Markov-chain Monte Carlo method

N J Camp et al. Am J Hum Genet. 2001 Dec.

Abstract

Palauans are an isolated population in Micronesia with lifetime prevalence of schizophrenia (SCZD) of 2%, compared to the world rate of approximately 1%. The possible enrichment for SCZD genes, in conjunction with the potential for reduced etiological heterogeneity and the opportunity to ascertain statistically powerful extended pedigrees, makes Palauans a population of choice for the mapping of SCZD genes. We have used a Markov-chain Monte Carlo method to perform a genomewide multipoint analysis in seven extended pedigrees from Palau. Robust multipoint parametric and nonparametric linkage (NPL) analyses were performed under three nested diagnostic classifications-core, spectrum, and broad. We observed four regions of interest across the genome. Two of these regions-on chromosomes 2p13-14 (for which, under core diagnostic classification, NPL=6.5 and parametric LOD=4.8) and 13q12-22 (for which, under broad diagnostic classification, parametric LOD=3.6, and, under spectrum diagnostic classification, parametric LOD=3.5)-had evidence for linkage with genomewide significance, after correction for multiple testing; with the current pedigree resource and genotyping, these regions are estimated to be 4.3 cM and 19.75 cM in size, respectively. A third region, with intermediate evidence for linkage, was identified on chromosome 5q22-qter (for which, under broad diagnostic classification, parametric LOD=2.5). The fourth region of interest had only borderline suggestive evidence for linkage (on 3q24-28; for this region, under broad diagnostic classification, parametric LOD=2.0). All regions exhibited evidence for genetic heterogeneity. Our findings provide significant evidence for susceptibility loci on chromosomes 2p13-14 and 13q12-22 and support both a model of genetic heterogeneity and the utility of a broader set of diagnostic classifications in the population from Palau.

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Figures

Figure 1
Figure 1
Multipoint parametric and nonparametric linkage scores across the genome (22 autosomes in chromosomal order) for core (a), spectrum (b), and broad (c) diagnostic classifications.
Figure 2
Figure 2
Recessive multipoint LOD traces for the five pedigrees with linkage to the region on chromosome 2
Figure 3
Figure 3
Recessive multipoint LOD traces for the four pedigrees with linkage to the region on chromosome 13
See this image and copyright information in PMC

References

Electronic-Database Information

    1. Center for Medical Genetics, Marshfield Medical Research Foundation, http://research.marshfieldclinic.org/genetics/
    1. Cooperative Human Linkage Center, The, http://lpg.nci.nih.gov/CHLC/
    1. Genome Database, The, http://gdbwww.gdb.org/ (for information on genetic mapping)
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for SCZD [MIM 181500])

References

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