Abstract
BackgroundThe 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.ResultsFor 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13040-015-0076-y) contains supplementary material, which is available to authorized users.
Highlights
The genetic background to bipolar disorder (BPD) has been attributed to different genetic and genomic risk factors
Given the complex nature of BPD we applied a screening process intended to select families presumed to carry a relatively strong genetic influence of risk to BPD (Fig. 1). In this process genotypic data from 3849 individuals in 637 nuclear and extended BP-pedigrees was downloaded from the National Institute of Mental Health (NIMH) Genetic Initiatives’ website [19] and screened with a genome-wide family-wise parametric linkage scan under different genetic models using GENEHUNTER [20]
Pedigrees were screened for stretches of homozygous genotypes (ROH), possibly indicating deletions, as this type of genetic polymorphism has been shown to have a suggestive role in the etiology of BPD [21]
Summary
The genetic background to bipolar disorder (BPD) has been attributed to different genetic and genomic risk factors. 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. Accumulating data demonstrates that BPD is a both clinically and genetically heterogeneous disorder with different risk factors in different subgroups and with a shared genetic overlap between different diagnoses of psychiatric disorders [5, 6]. The emerging picture further reveals that individual genetic risk loci contribute with relatively small effect.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
