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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

Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia

TL;DR: A combined genome-wide association study of bipolar disorder and schizophrenia cases versus controls and a direct comparison GWAS of SCZ cases indicates that combining diseases with similar genetic risk profiles improves power to detect shared risk loci and that future direct comparisons of BP and SCZ are likely to identify loci with significant differential effects.
Journal ArticleDOI

Childhood developmental abnormalities in schizophrenia: evidence from high-risk studies

TL;DR: A review of findings concerning childhood and adolescent development from 16 HR studies and compares them with findings from cohort, conscript, and family studies concludes that there may be other mechanisms involved in addition to having a parent with schizophrenia.
Journal ArticleDOI

A quantitative meta-analysis of population-based studies of premorbid intelligence and schizophrenia

TL;DR: Strong associations between premorbid IQ and risk for schizophrenia, and age of illness onset argue for a widespread neurodevelopmental contribution to schizophrenia that operates across the entire range of intellectual ability.
Journal ArticleDOI

Autoimmune diseases, bipolar disorder, and non-affective psychosis

TL;DR: The data suggest that autoimmune processes precede onset of schizophrenia, but also non-affective psychosis and bipolar disorder, as well as a small role for genetic linkage.
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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).