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A genome screen of 35 bipolar affective disorder pedigrees provides significant evidence for a susceptibility locus on chromosome 15q25-26.
Mol Psychiatry. 2009 May; 14(5):492-500.MP

Abstract

Bipolar affective disorder is a heritable, relatively common, severe mood disorder with lifetime prevalence up to 4%. We report the results of a genome-wide linkage analysis conducted on a cohort of 35 Australian bipolar disorder families which identified evidence of significant linkage on chromosome 15q25-26 and suggestive evidence of linkage on chromosomes 4q, 6q and 13q. Subsequent fine-mapping of the chromosome 15q markers, using allele frequencies calculated from our cohort, gave significant results with a maximum two-point LOD score of 3.38 and multipoint LOD score of 4.58 for marker D15S130. Haplotype analysis based on pedigree-specific, identical-by-descent allele sharing, supported the location of a bipolar susceptibility gene within the Z(max-1) linkage confidence interval of 17 cM, or 6.2 Mb, between markers D15S979 and D15S816. Non-parametric and affecteds-only linkage analysis further verified the linkage signal in this region. A maximum NPL score of 3.38 (P=0.0008) obtained at 107.16 cM (near D15S130), and a maximum two-point LOD score of 2.97 obtained at marker D15S1004 (affecteds only), support the original genome-wide findings on chromosome 15q. These results are consistent with four independent positive linkage studies of mood and psychotic disorders, and raise the possibility that a common gene for susceptibility to bipolar disorder, and other psychiatric disorders may lie in this chromosome 15q25-26 region.

Authors+Show Affiliations

Neuroscience Research Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18227837

Citation

McAuley, E Z., et al. "A Genome Screen of 35 Bipolar Affective Disorder Pedigrees Provides Significant Evidence for a Susceptibility Locus On Chromosome 15q25-26." Molecular Psychiatry, vol. 14, no. 5, 2009, pp. 492-500.
McAuley EZ, Blair IP, Liu Z, et al. A genome screen of 35 bipolar affective disorder pedigrees provides significant evidence for a susceptibility locus on chromosome 15q25-26. Mol Psychiatry. 2009;14(5):492-500.
McAuley, E. Z., Blair, I. P., Liu, Z., Fullerton, J. M., Scimone, A., Van Herten, M., Evans, M. R., Kirkby, K. C., Donald, J. A., Mitchell, P. B., & Schofield, P. R. (2009). A genome screen of 35 bipolar affective disorder pedigrees provides significant evidence for a susceptibility locus on chromosome 15q25-26. Molecular Psychiatry, 14(5), 492-500. https://doi.org/10.1038/sj.mp.4002146
McAuley EZ, et al. A Genome Screen of 35 Bipolar Affective Disorder Pedigrees Provides Significant Evidence for a Susceptibility Locus On Chromosome 15q25-26. Mol Psychiatry. 2009;14(5):492-500. PubMed PMID: 18227837.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A genome screen of 35 bipolar affective disorder pedigrees provides significant evidence for a susceptibility locus on chromosome 15q25-26. AU - McAuley,E Z, AU - Blair,I P, AU - Liu,Z, AU - Fullerton,J M, AU - Scimone,A, AU - Van Herten,M, AU - Evans,M R, AU - Kirkby,K C, AU - Donald,J A, AU - Mitchell,P B, AU - Schofield,P R, Y1 - 2008/01/29/ PY - 2008/1/30/pubmed PY - 2009/7/14/medline PY - 2008/1/30/entrez SP - 492 EP - 500 JF - Molecular psychiatry JO - Mol. Psychiatry VL - 14 IS - 5 N2 - Bipolar affective disorder is a heritable, relatively common, severe mood disorder with lifetime prevalence up to 4%. We report the results of a genome-wide linkage analysis conducted on a cohort of 35 Australian bipolar disorder families which identified evidence of significant linkage on chromosome 15q25-26 and suggestive evidence of linkage on chromosomes 4q, 6q and 13q. Subsequent fine-mapping of the chromosome 15q markers, using allele frequencies calculated from our cohort, gave significant results with a maximum two-point LOD score of 3.38 and multipoint LOD score of 4.58 for marker D15S130. Haplotype analysis based on pedigree-specific, identical-by-descent allele sharing, supported the location of a bipolar susceptibility gene within the Z(max-1) linkage confidence interval of 17 cM, or 6.2 Mb, between markers D15S979 and D15S816. Non-parametric and affecteds-only linkage analysis further verified the linkage signal in this region. A maximum NPL score of 3.38 (P=0.0008) obtained at 107.16 cM (near D15S130), and a maximum two-point LOD score of 2.97 obtained at marker D15S1004 (affecteds only), support the original genome-wide findings on chromosome 15q. These results are consistent with four independent positive linkage studies of mood and psychotic disorders, and raise the possibility that a common gene for susceptibility to bipolar disorder, and other psychiatric disorders may lie in this chromosome 15q25-26 region. SN - 1476-5578 UR - https://www.unboundmedicine.com/medline/citation/18227837/A_genome_screen_of_35_bipolar_affective_disorder_pedigrees_provides_significant_evidence_for_a_susceptibility_locus_on_chromosome_15q25_26_ L2 - http://dx.doi.org/10.1038/sj.mp.4002146 DB - PRIME DP - Unbound Medicine ER -