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Genome scan of pedigrees multiply affected with bipolar disorder provides further support for the presence of a susceptibility locus on chromosome 12q23-q24, and suggests the presence of additional loci on 1p and 1q.
Psychiatr Genet. 2003 Jun; 13(2):77-84.PG

Abstract

OBJECTIVE

To localize genes conferring susceptibility to bipolar affective disorder.

METHODS

Seven families were selected on the basis of containing multiple cases of bipolar affective disorder present in three or more generations, an absence of schizophrenia and unilineal transmission. DNA samples from these families were genotyped with 365 microsatellite markers spaced at approximately 10 cM intervals across the whole genome. All markers were subjected to initial two-point and three-point analyses using LOD score and model-free analysis. All regions producing a result significant at P<0.01 were then subjected to four-point LOD score analysis under the assumption of heterogeneity. RESULTSA four-point LOD score of 2.8 was obtained using a dominant model and including unipolar cases as affected in the region of D12S342. Four-point LOD scores of 2 were obtained around D1S243, D1S251 and D3S1265. The positive results around D1S243 were accounted for by a LOD score of 3.1 occurring in a single pedigree.

CONCLUSIONS

Since there has been previous strong support for linkage to the region of 12q23-q24 around D12S342, it now seems very probable that it does indeed contain a gene influencing susceptibility to bipolar affective disorder. Some evidence for linkage in the region of 1q near to D1S251 has been reported in one previous study. It therefore seems that this region of 1q and the region of 1p close to D1S243 may also harbour susceptibility genes.

Authors+Show Affiliations

Joint Academic Department of Psychological Medicine, St Bartholomew's and Royal London School of Medicine and Dentistry, London, UK. dcutis@hgmp.mrc.ac.ukNo 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

12782963

Citation

Curtis, David, et al. "Genome Scan of Pedigrees Multiply Affected With Bipolar Disorder Provides Further Support for the Presence of a Susceptibility Locus On Chromosome 12q23-q24, and Suggests the Presence of Additional Loci On 1p and 1q." Psychiatric Genetics, vol. 13, no. 2, 2003, pp. 77-84.
Curtis D, Kalsi G, Brynjolfsson J, et al. Genome scan of pedigrees multiply affected with bipolar disorder provides further support for the presence of a susceptibility locus on chromosome 12q23-q24, and suggests the presence of additional loci on 1p and 1q. Psychiatr Genet. 2003;13(2):77-84.
Curtis, D., Kalsi, G., Brynjolfsson, J., McInnis, M., O'Neill, J., Smyth, C., Moloney, E., Murphy, P., McQuillin, A., Petursson, H., & Gurling, H. (2003). Genome scan of pedigrees multiply affected with bipolar disorder provides further support for the presence of a susceptibility locus on chromosome 12q23-q24, and suggests the presence of additional loci on 1p and 1q. Psychiatric Genetics, 13(2), 77-84.
Curtis D, et al. Genome Scan of Pedigrees Multiply Affected With Bipolar Disorder Provides Further Support for the Presence of a Susceptibility Locus On Chromosome 12q23-q24, and Suggests the Presence of Additional Loci On 1p and 1q. Psychiatr Genet. 2003;13(2):77-84. PubMed PMID: 12782963.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genome scan of pedigrees multiply affected with bipolar disorder provides further support for the presence of a susceptibility locus on chromosome 12q23-q24, and suggests the presence of additional loci on 1p and 1q. AU - Curtis,David, AU - Kalsi,Gursharan, AU - Brynjolfsson,Jon, AU - McInnis,Melvin, AU - O'Neill,Jane, AU - Smyth,Ciaran, AU - Moloney,Eamonn, AU - Murphy,Patrice, AU - McQuillin,Andrew, AU - Petursson,Hannes, AU - Gurling,Hugh, PY - 2003/6/5/pubmed PY - 2004/3/31/medline PY - 2003/6/5/entrez SP - 77 EP - 84 JF - Psychiatric genetics JO - Psychiatr. Genet. VL - 13 IS - 2 N2 - OBJECTIVE: To localize genes conferring susceptibility to bipolar affective disorder. METHODS: Seven families were selected on the basis of containing multiple cases of bipolar affective disorder present in three or more generations, an absence of schizophrenia and unilineal transmission. DNA samples from these families were genotyped with 365 microsatellite markers spaced at approximately 10 cM intervals across the whole genome. All markers were subjected to initial two-point and three-point analyses using LOD score and model-free analysis. All regions producing a result significant at P<0.01 were then subjected to four-point LOD score analysis under the assumption of heterogeneity. RESULTSA four-point LOD score of 2.8 was obtained using a dominant model and including unipolar cases as affected in the region of D12S342. Four-point LOD scores of 2 were obtained around D1S243, D1S251 and D3S1265. The positive results around D1S243 were accounted for by a LOD score of 3.1 occurring in a single pedigree. CONCLUSIONS: Since there has been previous strong support for linkage to the region of 12q23-q24 around D12S342, it now seems very probable that it does indeed contain a gene influencing susceptibility to bipolar affective disorder. Some evidence for linkage in the region of 1q near to D1S251 has been reported in one previous study. It therefore seems that this region of 1q and the region of 1p close to D1S243 may also harbour susceptibility genes. SN - 0955-8829 UR - https://www.unboundmedicine.com/medline/citation/12782963/Genome_scan_of_pedigrees_multiply_affected_with_bipolar_disorder_provides_further_support_for_the_presence_of_a_susceptibility_locus_on_chromosome_12q23_q24_and_suggests_the_presence_of_additional_loci_on_1p_and_1q_ L2 - http://dx.doi.org/10.1097/01.ypg.0000056684.89558.d2 DB - PRIME DP - Unbound Medicine ER -