Bipolar disorder susceptibility region on chromosome 3q29 not confirmed in a case–control association study

Abstract

Objectives. We identified a bipolar disorder (BPD) susceptibility region on chromosome 3q29 in a genome-wide linkage scan ( (Biol Psychiatry 52: 40), NPL-score 4.09) and follow-up linkage analysis ( (J Psychiatr Res 38(3): 357), NPL-scores >3 with five markers). These findings were supported by further fine-mapping of this region ( (Eur Neuropsychopharmacol 17(6–7): 501)), finding NPL-scores >3.9 with SNPs (single nucleotide polymorphisms) spanning a region of 3.46 Mbp in BPD families. Since genetic association studies are more powerful than linkage studies for detecting susceptibility genes of small effect size, we aimed to replicate these findings in an independent case-control sample collected in London (UK) and Vienna (Austria). Methods. A total of 51 SNPs were genotyped using Sequenom MassARRAY^® iPLEX Gold and tested for association in a sample of 526 cases suffering from DSM-IV and/or ICD-10 diagnosis of BPD and 691 controls. Results. No genotypic and/or allelic association, as well as no haplotypic association, was found for any SNP after multiple testing correction. Conclusions. However, we cannot exclude the possibility that our sample might not have the power to detect rare variants associated with susceptibility to BPD.

Key words::

• Bipolar disorder
• association
• chromosome 3q29
• affective disorders
• genetics

Acknowledgements

The study was funded by the ‘Österreichische Nationalbank Jubiläumsfonds’ (N°12723 and N°5777), and by the ESF MNMI Programme and Austrian Science Fund (N°P7639). Dr Schosser was supported by an Erwin-Schrödinger-Fellowship (Ref. Nr. J2647) of the Austrian Science Funds and by a NIHR BRC Preparatory Clinician Scientist Fellowship. Dr Cohen-Woods was supported by a Medical Research Councl (MRC) UK PhD studentship and a NIHR BRC Postdoctoral Research Fellowship. The bipolar disorder case–control study (BACCS) collection was supported by GlaxoSmithKline, Research and Development.

Statement of interest

None to declare.