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Open AccessJournal ArticleDOI

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

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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Journal ArticleDOI

Apparent latent structure within the UK Biobank sample has implications for epidemiological analysis

TL;DR: It is found that major health outcomes appear geographically structured and that coincident structure in health outcomes and genotype data can yield biased associations, and that fine-scale structure is detectable in apparently homogeneous samples such as ALSPAC when measured very precisely, and remains detectable in UK Biobank despite conventional approaches to account for it.
References
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Journal ArticleDOI

Polygenic risk score and the psychosis continuum model.

TL;DR: This is the first study using polygenic risk score (PGRS) to investigate the localization of diagnostic subcategories along the entire psychosis spectrum.
Journal ArticleDOI

Polygenic associations of neurodevelopmental genes in suicide attempt

TL;DR: Novel genome-wide insights are suggested that suggest the importance of a polygenic neurodevelopmental etiology in SB, even in the absence of major psychiatric diagnoses.
Journal ArticleDOI

A Population-Based Study of Genetic Variation and Psychotic Experiences in Adolescents

TL;DR: The findings lend little support to the hypothesis that psychotic experiences in population-based samples of adolescents share a comparable genetic architecture to schizophrenia, or that utilizing a broader and more common phenotype of psychotic experiences will be an efficient approach to increase understanding of the genetic etiology of schizophrenia.
Journal ArticleDOI

Polygenic dissection of the bipolar phenotype

TL;DR: Genetic susceptibility influences at least two major domains of psychopathological variation in the schizophrenia–b bipolar disorder clinical spectrum: one that relates to expression of a ‘bipolar disorder-like’ phenotype and one that is associated with expression of ‘schizophrenia- like’ psychotic symptoms.
Journal ArticleDOI

Investigation of the genetic association between quantitative measures of psychosis and schizophrenia: a polygenic risk score analysis.

TL;DR: This study confirms the presence of a genetic risk for schizophrenia as categorical diagnostic trait, but does not find evidence for the genetic risk underlying quantitative schizophrenia symptom dimensions.
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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).