Archival ReportTwo-Dimensional Genome Scan Identifies Multiple Genetic Interactions in Bipolar Affective Disorder
Section snippets
Subject Selection and Pedigree Pruning
Pedigrees were ascertained and genotyped using the methods described in Supplement 1. Due to limitations in the linkage analysis program MERLIN (http://www.sph.umich.edu/csg/abecasis/Merlin/index.html) (25), 12 of the 65 pedigrees required trimming of nonessential pedigree members to facilitate a computational analysis of all available families. The reduced cohort consisted of 668 individuals who had completed a Diagnostic Interview for Genetic Studies (DIGS) (26) interview and 643 who had full
Univariate Nonparametric Linkage and Permutation Analysis
Nonparametric linkage analysis for the 373 autosomal and 18 chromosome X microsatellite markers yielded both Z scores and LOD scores that were highly correlated (r = .897). Z scores from single-point linkage analysis using the Sall allele sharing statistic across the genome are shown in Figure 1.
Nominal genome-wide significance was determined via pseudosimulation of 10,000 genome scans that showed that Z scores exceeding 2.8 and 2.5 were to be considered significant (p < .05) and suggestive (p
Discussion
Using a cohort of 65 extended bipolar disorder pedigrees, we have shown evidence for multiple susceptibility loci and a complex pattern of genetic interaction underlying the inheritance of bipolar disorder. Nonparametric linkage in the pooled cohort supports loci detected in five previously reported individual waves of parametric analysis of these families (4q34-35 [20, 24], 13q14 [21, 22], 9q31-33, and 19p13 [22]) and has revealed new loci not previously detected in this cohort under
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Synapse-to-Nucleus Signaling in Neurodegenerative and Neuropsychiatric Disorders
2019, Biological PsychiatryCitation Excerpt :The physiological and behavioral alterations of Anks1b mutant mice are consistent with the association of ANKS1B with human neuropsychiatric disorders. Genome-wide studies have revealed genetic variants in ANKS1B associated with bipolar disorder, pediatric obsessive-compulsive disorder, and antipsychotic treatment response (49–51). Rare copy number variants and SNPs in the ANKS1B gene are also found in autism spectrum disorder (ASD) (52,53).
Patterns and predictors of family environment among adolescents at high and low risk for familial bipolar disorder
2019, Journal of Psychiatric ResearchCitation Excerpt :Procedures are detailed elsewhere (Nurnberger et al., 2011; Perich et al., 2015). Offspring at high-risk (HR) for familial BD were identified from probands with BD type I (BD-I), BD type II (BD-II), or schizoaffective disorder bipolar type (SAB) in the NIMH Genetics Initiative bipolar sample and other genetics studies (e.g., Fullerton et al., 2010; McAuley et al., 2009), and from specialty clinics and publicity. Control offspring were recruited via parents from general practitioners, motor vehicle records, and advertising, excluding families with a parent with major mood, psychotic, or substance use disorders; psychiatric hospitalizations; or a first-degree relative with a history of psychosis or hospitalization for a mood disorder.
Traumatic Stress Interacts With Bipolar Disorder Genetic Risk to Increase Risk for Suicide Attempts
2017, Journal of the American Academy of Child and Adolescent PsychiatryCitation Excerpt :DSM-IV diagnosis was derived through the Diagnostic Interview for Genetic Studies (DIGS)29 and the Family Instrument for Genetic Studies (FIGS).30 BD-relatives were predominantly (88%) children of a proband with BD ascertained through the National Institute of Mental Health Genetics Initiative bipolar sample or similar genetic studies31-33; only 6% were siblings of a proband with BD, and 6% were second-degree relatives of a proband from multiplex families in which a first-degree relative with BP-I or SAB also existed. Control participants were in the same age range but had no first-degree relative with a DSM-IV diagnosis of BP-I or BP-II, SAB, recurrent major depression, schizophrenia, recurrent substance abuse, or any past psychiatric hospitalization; and no parent with a first-degree relative who had a past mood disorder hospitalization or history of psychosis.
MiRNA-206 and BDNF genes interacted in bipolar i disorder
2014, Journal of Affective DisordersCitation Excerpt :However, there are no identified genes that are shown to be definitively responsible for causing this disorder. It is therefore likely that each gene only contributes a small fraction to the overall risk, and interactions between genes of small effect may work in an additive or multiplicative fashion to contribute a larger proportion of the heritable component of the traits observed in BD (Carlborg and Haley, 2004; Fullerton et al., 2010). In this study, we did not observe individual effect of MIR206 rs16882131 or BDNF rs6265 on the susceptibility to BD-I and treatment response.
Agmatinase, an inactivator of the putative endogenous antidepressant agmatine, is strongly upregulated in hippocampal interneurons of subjects with mood disorders
2012, NeuropharmacologyCitation Excerpt :To our knowledge, this is the first report to show that this enzyme may be involved in the pathophysiology of depression. This observation is in line with many previous studies demonstrating that the gene locus, where the agmatinase gene is located, is linked to bipolar disorder and major depression (McGuffin et al., 2005; Taştemir et al., 2006; Demirhan et al., 2009; Kaneva et al., 2009; Fullerton et al., 2010). The gene encoding human agmatinase is a single-copy gene composed of eight exons spanning 12.6 kb on chromosome 1, starting at position 1p36.13 (www.uniprot.org/docs/humchr01).