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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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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

Genetic Relationships Between Schizophrenia, Bipolar Disorder, and Schizoaffective Disorder

TL;DR: New insights into genetic relationships between these disorders are expected as studies continue to increase in sample size and in technical and analytical sophistication, information on phenotypes beyond clinical diagnoses are increasingly incorporated, and approaches such as next-generation sequencing identify additional types of genetic risk variant.
Journal ArticleDOI

Molecular genetic evidence for overlap between general cognitive ability and risk for schizophrenia: A report from the Cognitive Genomics consorTium (COGENT)

TL;DR: Results provide molecular confirmation of the genetic overlap between SCZ and general cognitive ability, and may provide additional insight into pathophysiology of the disorder.
Journal ArticleDOI

Genetic predisposition to schizophrenia associated with increased use of cannabis

TL;DR: In a sample of 2082 healthy individuals, an association is shown between an individual’s burden of schizophrenia risk alleles and use of cannabis, suggesting that part of the association between schizophrenia and cannabis is due to a shared genetic aetiology.
Journal ArticleDOI

Polygenic dissection of major depression clinical heterogeneity

TL;DR: Polygenic features of major depressive disorder and two common clinical subtypes defined by symptom profiles in a large sample of adults with established diagnoses are examined, finding that subtypes are characterized by partially distinct polygenic liabilities and may represent more homogeneous phenotypes.
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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).