Nonparametric simulation-based statistical analyses for bipolar affective disorder locus on chromosome 21q22.3

John B J Kwok, Linda J. Adams, Judy A. Salmon, Jennifer A. Donald, Philip B. Mitchell, Peter R. Schofield*

*Corresponding author for this work

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    35 Citations (Scopus)


    Straub et al. [1994: Nat Genet 8:291-296] reported a candidate bipolar affective disorder (BAD) locus on chromosome 21q22.3. As a replication study, we analyzed 12 Australian BAD pedigrees for the presence of excess allele sharing and cosegregation with the putative chromosome 21q22.3 BAD locus, using six microsatellite markers. The nonparametric simulation-based statistic SimAPM produced positive results for the marker PFKL (P < 0.001) and D21S198 (P = 0.007). PFKL also demonstrated linkage (P < 0.001) when analyzed using the more conservative statistic, SimIBD. Comparable results were obtained when using the original APM statistic (P = 0.02 for D21S198). However, other nonparametric analyses such as GENEHUNTER and model-free linkage (MFLINK) analysis did not yield significant results. Combined LOD scores for the 12 families were strongly negative for all six markers under six genetic models. Two-point and multipoint analyses of individual families revealed one family, family 17, with maximal LOD scores greater than 1.41 for the 10.5-cM region between PFKL and D21S198. This report provides additional support for the suggestive linkage of a susceptibility locus for BAD on chromosome 21q22.3.

    Original languageEnglish
    Pages (from-to)99-102
    Number of pages4
    JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
    Issue number1
    Publication statusPublished - 5 Feb 1999


    • Bipolar affective disorder
    • Chromosome 21
    • Genetic linkage
    • Manic depressive illness


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