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The use of polygenic risk scores to identify phenotypes associated with genetic risk of schizophrenia: Systematic review.

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TLDR
Overall, SZ-PRS was associated with increased risk for psychiatric disorders such as depression and bipolar disorder, lower performance IQ and negative symptoms, and a framework is proposed to guide robust reporting of PRS associations in the future.
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This article is published in Schizophrenia Research.The article was published on 2017-11-10 and is currently open access. It has received 115 citations till now. The article focuses on the topics: Bipolar disorder & Schizophrenia.

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Citations
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Penetrance and pleiotropy of polygenic risk scores for schizophrenia in 90,000 patients across three healthcare systems

TL;DR: It is demonstrated that an available measure of genetic risk for schizophrenia is robustly associated with schizophrenia in healthcare settings and has pleiotropic effects on related psychiatric disorders as well as other medical symptoms and syndromes.
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The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study.

Diego Quattrone, +55 more
TL;DR: In this article, the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis was evaluated using data from the EU-GEI study.
Journal ArticleDOI

The relative and interactive impact of multiple risk factors in schizophrenia spectrum disorders: a combined register-based and clinical twin study

TL;DR: It is suggested that several risk factors contribute to increasing schizophrenia spectrum vulnerability and cannabis, a potentially completely avoidable environmental risk factor, seems to play a substantial role in schizophrenia pathology.
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The "missing heritability"-Problem in psychiatry: Is the interaction of genetics, epigenetics and transposable elements a potential solution?

TL;DR: In this paper, the authors argue that one possible solution to the missing heritability problem in psychiatry is a potential role of retrotransposons, the exploration of which is presently only in its beginnings.
Journal ArticleDOI

Profiling haplotype specific CpG and CpH methylation within a schizophrenia GWAS locus on chromosome 14 in schizophrenia and healthy subjects

TL;DR: The methylation profile associated with the schizophrenia risk haplotype within the KLC1 fourth intron and confirmed ASM for cytosines located in the vicinity of rs67899457 are determined and may be related to the pathophysiological mechanism differentiating the risk and non-risk haplotypes.
References
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Journal ArticleDOI

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

TL;DR: Moher et al. as mentioned in this paper introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses, which is used in this paper.
Journal Article

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement.

TL;DR: The QUOROM Statement (QUality Of Reporting Of Meta-analyses) as mentioned in this paper was developed to address the suboptimal reporting of systematic reviews and meta-analysis of randomized controlled trials.
Journal ArticleDOI

Biological insights from 108 schizophrenia-associated genetic loci

Stephan Ripke, +354 more
- 24 Jul 2014 - 
TL;DR: Associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses.
Journal ArticleDOI

The Endophenotype Concept in Psychiatry: Etymology and Strategic Intentions

TL;DR: The authors discuss the etymology and strategy behind the use of endophenotypes in neuropsychiatric research and, more generally, in research on other diseases with complex genetics.
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Frequently Asked Questions (9)
Q1. What are the contributions mentioned in the paper "The use of polygenic risk scores to identify phenotypes associated with genetic risk of schizophrenia: systematic review" ?

This paper conducted a systematic review to identify studies that have used a polygenic risk score ( PRS ) approach to examine phenotypes associated with genetic risk for schizophrenia. 

One of the main advantages of the PRS approach is the ability to study how genetic risk for schizophrenia is manifest across the general population, and during different stages of development. 

Future increases in size of discovery samples may also enable PRSs to make a meaningful contribution to risk prediction models, as has been shown for some non-psychiatric disorders (Chatterjee et al. 2016). 

The population-based Longitudinal Experiences and Perceptions (LEAP) study found that SZPRS was associated with decreased anhedonia (strongest PT<0.5; one-tailed p=0.003) and parent-rated negative symptoms in adolescence (one-tailed p=0.029) (Sieradzka et al. 2014). 

The SZ-PRS was consistently associated with poorer cognition in population-based studies and from childhood through to older age (McIntosh et al. 2013; Hubbard et al. 2016). 

In the Netherlands case-control study of schizophrenia, SZ-PRS was associated with five symptom dimensions (strongest PT<0.5): positive (p=<0.01), negative (p= <0.001), mania (p= <0.01), depression (p= <0.001) and disorganisation (p=0.04) within the combined casecontrol sample, but not with these dimensions in cases and controls examined separately (Derks et al. 2012). 

the inconsistency of reporting of results across studies meant that only a narrative approach to this review was feasible, and assessment of publication bias was not possible. 

The SZ-PRS was also associated with a number of other, non-psychiatric outcomes, including diabetes, RA and CD (Stringer et al. 2014), though results were not consistent across studies. 

Higher SZ-PRS was associated with lower total IQ in a combined schizophrenia case–control sample (strongest PT<0.3, p=8x10-4), but this was attenuated when analysing cases only (p=0.067), with no association in controls (van Scheltinga et al. 2013).