Identification of susceptibility loci at 7q31 and 9p13 for bipolar disorder in an isolated population

Abstract

We performed a linkage analysis on 23 Finnish families with bipolar disorder and originating from the North-Eastern region of Finland, using the Illumina Linkage Panel IV (6K) Array with an average intermarker spacing of 0.65 cM across the genome. We detected genome-wide significant evidence for linkage of mood disorder (bipolar disorder type I, II, or not otherwise specified, manic type of schizoaffective psychosis, cyclothymia, or recurrent depression) to chromosomes 7q31 (LOD = 3.20) and 9p13.1 (LOD = 4.02). Analyzing the best markers on the complete set of 179 Finnish bipolar families supported the findings on chromosome 9p13 (maximum LOD score of 3.02 at position 383 Mb, immediately upstream of the centromere). This region harbors several interesting candidate genes, including contactin associated protein-like 3 (CNTNAP3) and aldehyde dehydrogenase 1 (ALDH1B1). For the 7q31 locus, only one extended pedigree and ten families originating from the same late settlement region in North-Eastern Finland provided evidence for linkage, suggesting that a gene predisposing to bipolar disorder is enriched in that region. Candidate genes of interest in this locus include potassium-voltage-gated channel, member 2 (KCND2) and calcium-dependent activator protein for secretion 2 (CADPS2). The loci on the centromeric region of 9p13 and the telomeric region of 7q31 may represent susceptibility loci for mood disorder in the Finnish population.

Human ALDH1B1 Polymorphisms may Affect the Metabolism of Acetaldehyde and All-trans retinaldehyde—In Vitro Studies and Computational Modeling

“…Some of these include: increased risk for certain cancers and myocardial infarction with polymorphisms of ALDH2 (45-48); increased risk of spina bifida with polymorphisms of ALDH1A2 (49); γ-hydroxybutyric aciduria with polymorphisms of ALDH5A1 (50); developmental and metabolic abnormalities with polymorphisms of ALDH6A1 (51); and Sjögren-Larsson syndrome with polymorphisms of ALDH3A2 (52). Finally, a linkage analysis of Finnish families identified two chromosomal regions associated with bipolar disorder, 9p13.1, which contains ALDH1B1, among other candidate enzymes, and 7q31 (53). Given the proposed roles for ALDH1B1, it is no surprise that polymorphisms with diminished catalytic activity could have significant pathophysiological consequences.…”

Candidate Hippocampal Biomarkers of Susceptibility and Resilience to Stress in a Rat Model of Depression

“…Moreover, hippocampal neurogenesis and differentiation may be linked with depression (43), suggesting that stress-induced perturbed CADPS2 levels may occur in depressive disorder. Interestingly, the Cadps2 gene has also been associated with bipolar disorder (52).…”

Effect of Schizophrenia Risk-Associated Alleles in SREB2 (GPR85) on Functional MRI Phenotypes in Healthy Volunteers

“…Our data would seem to fit in the affective disorders more than the schizophrenia pattern, although considerable genetic overlap between bipolar disorder and schizophrenia has been reported (Lichtenstein et al, 2009). We are not aware of any studies linking SREB2 to mood or anxiety disorders, with the possible exception of Palo et al (2010), but it should be kept in mind that the SNPs explored here were only very recently added to public databases and are therefore unlikely to be found on the chips commonly used for large genome-wide studies. Moreover, they are not in the Hapmap database and were therefore not imputed in prior studies.…”