Genome-wide scan in Portuguese Island families implicates multiple loci in bipolar disorder : fine mapping adds support on chromosomes 6 and 11

As part of an extensive study in the Portuguese Island population of families with multiple patients suffering from bipolar disorder and schizophrenia, we performed an initial genome-wide scan of 16 extended families with bipolar disorder that identified three regions on chromosomes 2, 11, and 19 wi...

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Bibliographic Details
Main Author: Pato, Carlos N. (author)
Other Authors: Pato, Michele T. (author), Kirby, A. N. (author), Petryshen, T. L. (author), Medeiros, Helena (author), Carvalho, Célia (author), Macedo, António (author), Dourado, A. (author), Coelho, I. (author), Valente, J. (author), Soares, M. J. (author), Ferreira, Carlos Paz (author), Lei, M. (author), Verner, A. (author), Hudson, T. J. (author), Morley, C. P. (author), Kennedy, J. L (author), Azevedo, Maria H. (author), Daly, M. J. (author), Sklar, P. (author)
Format: article
Language:eng
Published: 2017
Subjects:
Bipolar Disorder
Schizophrenia
Online Access:http://hdl.handle.net/10400.3/3998
Country:Portugal
Oai:oai:repositorio.uac.pt:10400.3/3998
Description
Summary:As part of an extensive study in the Portuguese Island population of families with multiple patients suffering from bipolar disorder and schizophrenia, we performed an initial genome-wide scan of 16 extended families with bipolar disorder that identified three regions on chromosomes 2, 11, and 19 with genome-wide suggestive linkage and several other regions, including chromosome 6q, also approached suggestive levels of significance. Dick et al. [2003: Am J Hum Genet 73:107-114] recently reported in a study of 250 families with bipolar disorder a maxLOD score of 3.61 near marker D6S1021 on chromosome 6q. This study replicates this finding having detected a peak NPL = 2.02 (P = 0.025) with the same marker D6S1021(104.7 Mb). Higher-density mapping provided additional support for loci on chromosome 6 including marker D6S1021 with an NPL = 2.59 (P = 0.0068) and peaking at marker D6S1639 (125 Mb) with an NPL = 3.06 (P = 0.0019). A similar pattern was detected with higher-density mapping of chromosome 11 with an NPL = 3.15 (P = 0.0014) at marker D11S1883 (63.1 Mb). Simulations at the density of our fine mapping data indicate that less than 1 scan out of 10 would find two such scores genome-wide in the same scan by chance. Our findings provide additional support for a susceptibility locus for bipolar disorder on 6q, as well as, suggesting the importance of denser scans.

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