A population-based heritability estimate of bipolar disorder – In a Swedish twin sample

Johansson, Viktoria; Kuja‐Halkola, Ralf; Cannon, Tyrone D.; Hultman, Christina M.; Hedman, Anna M.

doi:10.1016/j.psychres.2019.06.010

Cited by 83 publications

(38 citation statements)

References 43 publications

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“…Psychiatric and neurological disorders that share difficulties with sociability as a common feature are known to be heritable (estimates are ~64-91% for ASD (Sandin et al, 2017), ~30-40% for MDD (Sullivan, Neale, & Kendler, 2000), ~79% for SCZ (Hilker et al, 2018), ~60% for BP (Johansson, Kuja-Halkola, Cannon, Hultman, & Hedman, 2019), ~60-80 for AD (Gatz et al, 2006). Genome-wide association studies (GWAS) are the current gold standard for localizing common genetic risk variants important for these disorders, comparing people with the disorder (cases) to people without the disorder (controls).…”

Section: Introductionmentioning

confidence: 99%

Genetic underpinnings of sociability in the UK Biobank

Bralten

Klemann

Mota

et al. 2019

Preprint

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Difficulties with sociability include a tendency to avoid social contacts and activities, and to prefer being alone rather than being with others. While sociability is a continuously distributed trait in the population, decreased sociability represent a common early manifestation of multiple neuropsychiatric disorders such as Schizophrenia (SCZ), Bipolar Disorder (BP), Major Depressive Disorder (MDD), Autism Spectrum Disorders (ASDs), and Alzheimer's disease (AD). We aimed to investigate the genetic underpinnings of sociability as a continuous trait in the general population. In this respect, we performed a genome-wide association study (GWAS) using a sociability score based on 4 social functioning-related self-report questions in the UK Biobank sample (n=342,461) to test the effect of individual genetic variants. This was followed by LD score analyses to investigate the genetic correlation with psychiatric disorders (SCZ, BP, MDD, ASDs) and a neurological disorder (AD) as well as related phenotypes (Loneliness and Social Anxiety). The phenotypic data indeed showed that the sociability score was decreased in individuals with ASD, (probable) MDD, BP and SCZ, but not in individuals with AD. Our GWAS showed 604 genome-wide significant SNPs, coming from 18 independent loci (SNP-based h2=0.06). Genetic correlation analyses showed significant correlations with SCZ (rg=0.15, p=9.8e-23), MDD (rg=0.68, and ASDs (rg=0.27,, but no correlation with BP (rg=0.01, p=0.45) or AD (rg=0.04, p=0.55). Our sociability trait was also genetically correlated with Loneliness (rg=0.45, p=2.4e-8) and Social Anxiety (rg=0.48, p=0.002). Our study shows that there is a significant genetic component to variation in population levels of sociability, which is relevant to some psychiatric disorders (SCZ, MDD, ASDs), but not to BP and AD.

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Section: Introductionmentioning

confidence: 99%

Genetic underpinnings of sociability in the UK Biobank

Bralten

Klemann

Mota

et al. 2019

Preprint

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“…Taking twin studies into consideration, transmissibility of BD is likely to be >60%, one of the highest among psychiatric disorders. 22 It is postulated that deregulation of gene function instigated by alterations, polymorphisms, and epigenetic modifications influence particular cellular signaling cascades, contributing towards disease onset and progression. The genetic vulnerability in BD is expressed as a pheno-type, influenced by epigenetic changes and stressful life circumstances.…”

Section: Geneticsmentioning

confidence: 99%

“…Taking twin studies into consideration, transmissibility of BD is likely to be >60%, one of the highest among psychiatric disorders. 22 …”

Section: Candidate Biomarkersmentioning

confidence: 99%

The Discovery of Clinically Applicable Biomarkers for Bipolar Disorder: A Review of Candidate and Proteomic Approaches

Muneer

2020

Chonnam Med J

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Bipolar disorder (BD) is a severe psychiatric condition which affects innumerable people across the globe. The etiopathogenesis of BD is multi-faceted with genetic, environmental and psychosocial factors playing a role. Hitherto, the diagnosis and management of BD are purely on empirical grounds as we lack confirmed biomarkers for this condition. In this regard, hypothesis-driven investigations have been unable to identify clinically applicable biomarkers, steering the field towards newer technologies. Innovative, state-of-the-art techniques like multiplex immunoassays and mass spectrometry can potentially investigate the entire proteome. By detecting up or down regulated proteins, novel biomarkers are identified and new postulates about the etiopathogenesis of BD are specified. Hence, biological pathways are uncovered which are involved in the initiation and advancement of the disease and new therapeutic targets are identified. In this manuscript, the extant literature is thoroughly reviewed and the latest findings on candidate BD biomarkers are provided, followed by an overview of the proteomic approaches. It was found that due to the heterogeneous nature of BD no single biomarker is feasible, instead a panel of tests is more likely to be useful. With the application of latest technologies, it is expected that validated biomarkers will be discovered which will be useful as diagnostic tools and help in the delivery of individually tailored therapies to the patients.

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“…The etiology and pathophysiology of BD is complex and far from understood ( 13 ). BD is one of the most heritable psychiatric disorders, with an estimated heritability of 60–85%, though both genetic and environmental factors influence risk ( 14 – 16 ). Thus far, 30 genome-wide significant loci have been identified in BD, containing genes encoding ion channels, neurotransmitter transporters and synaptic components ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

Lithium and the Interplay Between Telomeres and Mitochondria in Bipolar Disorder

et al. 2020

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Bipolar disorder is a severe psychiatric disorder which affects more than 1% of the world’s population and is a leading cause of disability among young people. For the past 50 years, lithium has been the drug of choice for maintenance treatment of bipolar disorder due to its potent ability to prevent both manic and depressive episodes as well as suicide. However, though lithium has been associated with a multitude of effects within different cellular pathways and biological systems, its specific mechanism of action in stabilizing mood remains largely elusive. Mitochondrial dysfunction and telomere shortening have been implicated in both the pathophysiology of bipolar disorder and as targets of lithium treatment. Interestingly, it has in recent years become clear that these phenomena are intimately linked, partly through reactive oxygen species signaling and the subcellular translocation and non-canonical actions of telomerase reverse transcriptase. In this review, we integrate the current understanding of mitochondrial dysfunction, oxidative stress and telomere shortening in bipolar disorder with documented effects of lithium. Moreover, we propose that lithium’s mechanism of action is intimately connected with the interdependent regulation of mitochondrial bioenergetics and telomere maintenance.

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A population-based heritability estimate of bipolar disorder – In a Swedish twin sample

Cited by 83 publications

References 43 publications

Genetic underpinnings of sociability in the UK Biobank

Genetic underpinnings of sociability in the UK Biobank

The Discovery of Clinically Applicable Biomarkers for Bipolar Disorder: A Review of Candidate and Proteomic Approaches

Lithium and the Interplay Between Telomeres and Mitochondria in Bipolar Disorder

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