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BioData Min. 2015 Dec 18;8:42. doi: 10.1186/s13040-015-0076-y. eCollection 2015.

A significant risk locus on 19q13 for bipolar disorder identified using a combined genome-wide linkage and copy number variation analysis.

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Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Department of Mathematics, Division of Mathematical Statistics, Stockholm University, SE-106 91 Stockholm, Sweden.



The genetic background to bipolar disorder (BPD) has been attributed to different genetic and genomic risk factors. In the present study we hypothesized that inherited copy number variations (CNVs) contribute to susceptibility of BPD. We screened 637 BP-pedigrees from the NIMH Genetic Initiative and gave priority to 46 pedigrees. In this subsample we performed parametric and non-parametric genome-wide linkage analyses using ~21,000 SNP-markers. We developed an algorithm to test for linkage restricted to regions with CNVs that are shared within and across families.


For the combined CNV and linkage analysis, one region on 19q13 survived correction for multiple comparisons and replicates a previous BPD risk locus. The shared CNV map to the pregnancy-specific glycoprotein (PSG) gene, a gene-family not previously implicated in BPD etiology. Two SNPs in the shared CNV are likely transcription factor binding sites and are linked to expression of an F-box binding gene, a key regulator of neuronal pathways suggested to be involved in BPD etiology.


Our CNV-weighted linkage approach identifies a risk locus for BPD on 19q13 and forms a useful tool to future studies to unravel part of the genetic vulnerability to BPD.


Bipolar disorder; Copy number variation; Genome-wide; Linkage analysis

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