Association of Variants in DISC1 With Psychosis-Related Traits in a Large Population Cohort

Tomppo, Liisa; Hennah, William; Miettunen, Jouko; Järvelin, Marjo‐Riitta; Veijola, Juha; Ripatti, Samuli; Lahermo, Päivi; Lichtermann, Dirk; Peltonen, Leena; Ekelund, Jesper

doi:10.1001/archgenpsychiatry.2008.524

Cited by 51 publications

(45 citation statements)

References 48 publications

(73 reference statements)

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“…Meanwhile, an association between the Disrupted In Schizophrenia gene and the social anhedonia trait, a cardinal symptom of schizophrenia spectrum disorder, has been reported [34]. Variants of the p250 guanosine triphosphatase-activating protein gene have been found to play a role in the negative schizotypy dimension and interpersonal schizotypy factors [15].…”

Section: Schizotypal Personality Disordermentioning

confidence: 99%

Genetic and Neuroimaging Features of Personality Disorders: State of the Art

Fan

Shen

et al. 2016

Neurosci. Bull.

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Personality disorders often act as a common denominator for many psychiatric problems, and studies on personality disorders contribute to the etiopathology, diagnosis, and treatment of many mental disorders. In recent years, increasing evidence from various studies has shown distinctive features of personality disorders, and that from genetic and neuroimaging studies has been especially valuable. Genetic studies primarily target the genes encoding neurotransmitters and enzymes in the serotoninergic and dopaminergic systems, and neuroimaging studies mainly focus on the frontal and temporal lobes as well as the limbic-paralimbic system in patients with personality disorders. Although some studies have suffered due to unclear diagnoses of personality disorders and some have included few patients for a given personality disorder, great opportunities remain for investigators to launch new ideas and technologies in the field.

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Section: Schizotypal Personality Disordermentioning

confidence: 99%

Genetic and Neuroimaging Features of Personality Disorders: State of the Art

Fan

Shen

et al. 2016

Neurosci. Bull.

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“…16,26,[36][37][38] Association of DISC1 with psychosis-related traits has been reported in Finnish population. 39 A genome-wide association study has shown nominal association for SCZ with the SNPs near the DISC1 translocation break point. 40 These results support a role for TSNAX/DISC1 genetic variation in conferring susceptibility to both SCZ and BPAD.…”

Section: Introductionmentioning

confidence: 99%

Gender-specific association of TSNAX/DISC1 locus for schizophrenia and bipolar affective disorder in South Indian population

et al. 2012

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Genetic association studies have implicated the TSNAX/DISC1 (disrupted in schizophrenia 1) in schizophrenia (SCZ), bipolar affective disorder (BPAD) and major depression. This study was performed to assess the possible involvement of TSNAX/DISC1 locus in the aetiology of BPAD and SCZ in the Southern Indian population. We genotyped seven single nucleotide polymorphism (SNPs) from TSNAX/DISC1 region in 1252 individuals (419 BPAD patients, 408 SCZ patients and 425 controls). Binary logistic regression revealed a nominal association for rs821616 in DISC1 for BPAD and also combined cases of BPAD or SCZ, but after correcting for multiple testing, these results were non-significant. However, significant association was observed with BPAD, as well as combined cases of BPAD or SCZ, within the female subjects for the rs766288 after applying false discovery rate corrections at the 0.05 level. Two-locus analysis showed C-C (rs766288-rs2812393) as a risk combination in BPAD, and G-T (rs2812393-rs821616) as a protective combination in SCZ and combined cases of BPAD or SCZ. Female-specific associations were observed for rs766288-rs2812393, rs766288-rs821616 and rs8212393-rs821616 in two-locus analysis. Our results provide further evidence for sex-dependent effects of the TSNAX/DISC1 locus in the aetiology of SCZ and BPAD. INTRODUCTION Schizophrenia (SCZ) and bipolar affective disorder (BPAD) are severe psychiatric disorders, each affecting approximately 1% of the population worldwide. 1 Family, twin and adoption studies confirm that genetic factors have a significant role in the aetiology of these disorders. 2 Several putative susceptibility loci and genes have been implicated, of which the TSNAX/DISC1 locus has shown encouraging results. The gene disrupted in schizophrenia 1 (DISC1) was first identified in a large Scottish family with a balanced translocation t (1, 11) (q42.2, q14.3) segregating with major mental illness, including SCZ, BPAD and recurrent major depression. [3][4][5] The translinassociated factor X (TRAX; TSNAX) gene is located adjacent to the DISC1 towards the 5 0 region. Subsequently several linkage studies have observed linkage near 1q42, which harbours DISC1, to SCZ 6-9 and BPAD. 10-12 Several population-based and family-based association studies have supported the role of the TSNAX/DISC1 locus in SCZ and/or BPAD in Caucasian 13-25 and Asian 26-28 populations. However, other studies have failed to replicate association between TSNAX/DISC1

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“…These risk alleles have previously been associated with schizophrenia, bipolar disorder, and social and physical anhedonia, mainly in females. 1,7 Reports suggest that heritability of neuroticism, anxiety and depression is higher in females than in males, and that the genes involved differ between men and women. [8][9][10] We tested SNPs and models specifically chosen on the basis of earlier evidence, and hence do not believe that stringent multiple testing corrections are appropriate, but these results need to be replicated in other suitable cohorts before variation in DISC1 is fully accepted as contributing to normal variation in neuroticism and mood.…”

mentioning

confidence: 99%

“…The discovery of a novel FAD-dependent protein, renalase, was reported in 2005. 7 Renalase was identified using an in silico approach that aimed to discover novel proteins secreted by the kidney. The renalase protein sequence contains a highly conserved N-terminal FAD-binding domain and an amine oxidoreductase domain.…”

mentioning

confidence: 99%

“…8 Recombinant renalase was shown to generate hydrogen peroxide in the presence of monoamines (including catecholamines), suggesting that it may share the catecholamine-degrading activity of MAO-A and B. 7 This activity was greatest in the presence of dopamine (followed by adrenaline and noradrenaline), 7 but it was not inhibited by MAO inhibitors, indicating differences in the possible catecholamine-degrading actions of these proteins.…”

mentioning

confidence: 99%

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Variation in DISC1 is associated with anxiety, depression and emotional stability in elderly women

et al. 2010

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Association of Variants in DISC1 With Psychosis-Related Traits in a Large Population Cohort

Abstract: Variants in DISC1 affect the level of social anhedonia, a cardinal symptom of schizophrenia in the general population. DISC1 might be more central to human psychological functioning than previously thought, as it seems to affect the degree to which people enjoy social interactions.

Cited by 51 publications

References 48 publications

Genetic and Neuroimaging Features of Personality Disorders: State of the Art

Genetic and Neuroimaging Features of Personality Disorders: State of the Art

Gender-specific association of TSNAX/DISC1 locus for schizophrenia and bipolar affective disorder in South Indian population

Variation in DISC1 is associated with anxiety, depression and emotional stability in elderly women

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