ABSTRACT
BACKGROUND: Oxytocin (OXT) and prolactin (PRL) are neuropeptide hormones that interact with the serotonin system and are involved in the stress response and social affiliation. In human studies, serum OXT and PRL levels have been associated with depression and related phenotypes. Our purpose was to determine if single nucleotide polymorphisms (SNPs) at the loci for OXT, PRL and their receptors, OXTR and PRLR, were associated with childhood-onset mood disorders (COMD). METHODS: Using 678 families in a family-based association design, we genotyped 16 SNPs at OXT, PRL, OXTR and PRLR to test for association with COMD. RESULTS: No significant associations were found for SNPs in the OXTR, PRL, or PRLR genes. Two of three SNPs 3' of the OXT gene were associated with COMD (p≤0.02), significant after spectral decomposition, but were not significant after additionally correcting for the number of genes tested. Supplementary analyses of parent-of-origin and proband sex effects for OXT SNPs by Fisher's Exact test were not significant after Bonferroni correction. CONCLUSIONS: We have examined 16 OXT and PRL system gene variants, with no evidence of statistically significant association after correction for multiple tests.
Subject(s)
Mood Disorders/genetics , Oxytocin/genetics , Polymorphism, Single Nucleotide , Prolactin/genetics , Adolescent , Age of Onset , Child , Family , Female , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Male , Mood Disorders/epidemiology , Receptors, Oxytocin/genetics , Receptors, Prolactin/geneticsABSTRACT
The chromosome 13q region has been linked to bipolar disorder in a number of genome scans as well as focused linkage studies. Previously we identified linkage to the 13q32 region in a genome scan of 146 affected sibling pair families from Hungary with juvenile-onset mood disorders. Within this region are the overlapping genes G72/G30, with G72 now officially named as D-amino-acid oxidase activator (DAOA). This locus has been associated with panic disorder, schizophrenia, and bipolar disorder. In this study, we tested for association to 11 markers in these genes and mood disorders in a sample of 646 nuclear families identified with a proband with onset of a mood disorder before 14.9 years of age. We identified evidence for association to three markers within the gene (rs2391191, rs3918341, rs1935062), two of which had been associated with bipolar disorder in previous studies. When corrected for the number of markers tested, the results were no longer significant, however the prior evidence for association of this gene in multiple studies points to this gene as a potential contributor to juvenile-onset mood disorders.
Subject(s)
D-Amino-Acid Oxidase/genetics , Mood Disorders/enzymology , Mood Disorders/genetics , Adolescent , Age of Onset , Child , Gene Expression Regulation , Gene Frequency/genetics , Genetic Predisposition to Disease , Humans , Hungary/epidemiology , Linkage Disequilibrium/genetics , Meta-Analysis as Topic , Mood Disorders/epidemiology , Polymorphism, Single Nucleotide/geneticsABSTRACT
Mood disorders (bipolar and depressive disorders) in children and adolescents are associated with significant morbidity and mortality. Twin and family studies, for the most part, indicate higher familiality and heritability for mood disorders that onset in childhood/adolescence than those that onset in adulthood. To identify the genetic contribution to mood disorders that onset in childhood/adolescence, we performed a genome scan on 146 nuclear families from Hungary containing an affected proband and affected siblings. In total, the pedigrees contained 303 affected children: 146 probands, 137 siblings with a first episode of mood disorder before 14.9 years of age, and 20 siblings with onset of their first episode after 14.9 years of age but before the age of 18. The results of the genome scan using 405 microsatellite markers did not provide evidence for linkage at the recommended genome wide significance level for any novel loci. However, markers on two chromosomes, 13q and Xq, provided evidence for linkage in regions previously identified as linked to bipolar disorder in multiple studies. For the marker on chromosome 13q the peak non-parametric multipoint LOD score was at the marker D13S779 (LOD = 1.5, P = 0.004). On chromosome Xq, evidence for linkage was observed across a large region spanning two regions previously linked to bipolar disorder; Xq24 to Xq28, with a peak at marker TTTA062 (LOD 2.10, P = 0.0009) in Xq28. Results for these regions exceed the recommended P-value for a replication study of P < 0.01 and thus provide evidence for these two loci as contributing to mood disorders with juvenile onset.
