title: A significant risk locus on 19q13 for bipolar disorder identified using a combined genome-wide linkage and copy number variation analysis.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Lekman
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Karlsson
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lisette
authors.initials: L
authors.lastname: Graae
authors.affiliation: Department of Mathematics, Division of Mathematical Statistics, Stockholm University, SE-106 91 Stockholm, Sweden.
authors.forename: Ola
authors.initials: O
authors.lastname: Hössjer
authors.affiliation: Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kockum
keywords: Bipolar disorder; Copy number variation; Genome-wide; Linkage analysis