Genome scan in sibling pairs with juvenile‐onset mood disorders: Evidence for linkage to 13q and Xq

Abstract

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.

Sex-specific rates of transmission of psychosis in the New England high-risk family study

“…In addition, the protocadherin 11 X-linked (PCDH11X) gene has been proposed in the etiology of psychosis (Crow, 2008). Further, the distal long arm (q) of the X chromosome has been linked to schizophrenia spectrum diagnoses in females with Fragile X syndrome (Reiss et al, 1988), juvenile-onset mood disorders (Wigg et al, 2009), bipolar and related affective disorders, such as schizoaffective bipolar disorder (Del Zompo et al, 1984; Zandi et al, 2003; Mendlewicz et al, 1980; Baron et al, 1987), suggesting that polymorphisms in this region of the X chromosome may be associated with psychosis in general rather than specific to schizophrenia. Interestingly, rare variants in microRNA genes, which negatively regulate gene expression, located on the X chromosome were implicated in SCZ risk (Feng et al, 2009).…”

Serotonin receptor 2C and mental disorders: Genetic, expression, and RNA editing studies

“…In addition, chromosomal location of HTR2C, Xq24, has been reported as the susceptibility loci for BD in linkage studies. 5,6 In animal models, mice deficient for Htr2c showed overweight by abnormal feeding behavior, and were prone to spontaneous death by seizures. 7 In addition, several behavioral alterations have been reported in this mice, such as enhanced exploration of a novel environment, increased sensitivity to the locomotor stimulant effects of cocaine, 8 dysregulation of sleep patterns, 9 and dysregulation of anxiety-related behaviors.…”

Revisiting Schizophrenia Linkage Data in the NIMH Repository: Reanalysis of Regularized Data Across Multiple Studies

“…Quite interestingly, however, all three locations identified in the families with Schizophrenia/Affective (11p15.3, 11p11.2, and Xq26.1) have been previously implicated in linkage or association studies using samples with bipolar disorder or mixed samples with schizophrenia and bipolar disorder (36–40). The 11p15.3 region was also reported as a main finding in the original publication for Study 7 (9), and indeed the African American-specific PPL reaches 15% at 28 cM.…”