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Identifying bipolar disorder susceptibility loci in a densely affected pedigree

Molecular Psychiatry volume 18, pages 1245–1246 (2013)Cite this article

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Bipolar disorder (BIP) is a highly heritable disorder with complex patterns of genetic inheritance, and recent genetic findings highlight the role of numerous common variants each with subtle effects.1 The existence of Mendelian subtypes of BIP (rare variants of very strong effects) has been postulated, particularly as such variants could prove to be more tractable for subsequent biological investigation.2 One way to evaluate this hypothesis is via the study of pedigrees densely affected with BIP, in which a genetic variant of strong effect inherited from a common ancestor may be more likely. With the advent of high-throughput technologies, we can now search densely affected pedigrees for specific variants that may contribute to risk for BIP.

First, we used genome-wide linkage analysis and an affected-only approach to identify genomic regions sharing identity-by-descent. Linkage analysis was performed using microsatellite data from 13 individuals.3 We used data from Illumina HumanOmni Quad genotyping arrays to identify shared segments using Beagle,4 Germline,5 PedIBD6 and runs of identity-by-state.7 Regions identified by linkage or with two sharing methods were considered candidate regions (Supplementary Table S2, six regions totaling 93.7 Mb).

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Acknowledgements

This study was funded by a NARSAD Distinguished Investigator Award (to PFS).

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Author notes

  1. M M Nöthen, M Rietschel and P F Sullivan: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill,, NC, USA

    A L Collins, Y Kim, J P Szatkiewicz, R J Bloom, C E Hilliard, C R Quackenbush & P F Sullivan

  2. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany

    S Meier & M Rietschel

  3. Civil Hospital, Carlos Haya, Malaga, Spain

    F Rivas & F Mayoral

  4. Department of Genomics, Institute of Human Genetics, University of Bonn, Bonn, Germany

    S Cichon & M M Nöthen

  5. Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    P F Sullivan

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  1. A L Collins
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  2. Y Kim
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  11. M M Nöthen
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  13. P F Sullivan
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Corresponding author

Correspondence to P F Sullivan.

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Competing interests

Dr Sullivan was on the SAB of Expression Analysis (Durham, NC, USA). The other authors report no conflict of interests.

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Collins, A., Kim, Y., Szatkiewicz, J. et al. Identifying bipolar disorder susceptibility loci in a densely affected pedigree. Mol Psychiatry 18, 1245–1246 (2013). https://doi.org/10.1038/mp.2012.176

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