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Biol Psychiatry. 2017 Mar 15;81(6):470-477. doi: 10.1016/j.biopsych.2016.06.028. Epub 2016 Aug 6.

An Examination of Polygenic Score Risk Prediction in Individuals With First-Episode Psychosis.

Author information

1
Medical Research Council, Social, Genetic & Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom. Electronic address: evangelos.vassos@kcl.ac.uk.
2
Medical Research Council, Social, Genetic & Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Departments of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
3
Medical Research Council, Social, Genetic & Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
4
Departments of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
5
Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
6
Medical Research Council, Social, Genetic & Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; National Institute for Health Research Mental Health Biomedical Research Centre, South London and Maudsley National Health Service Foundation Trust and King's College London, London, United Kingdom.
7
Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
8
Department of Medical and Molecular Genetics, King's College London, London, United Kingdom.
9
Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
10
Medical Research Council, Social, Genetic & Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada.
11
Basic and Clinical Neuroscience; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
12
School of Psychology, University of Sussex, Brighton and Sussex Partnership National Health Service Foundation Trust, West Sussex.
13
Departments of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; South London and Maudsley National Health Service Foundation Trust, London; United Kingdom.
14
Departments of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; National Institute for Health Research Mental Health Biomedical Research Centre, South London and Maudsley National Health Service Foundation Trust and King's College London, London, United Kingdom.
15
Department of Clinical Neurosciences, Neurology Unit, University of Cambridge, Cambridge, United Kingdom.

Abstract

BACKGROUND:

Polygenic risk scores (PRSs) have successfully summarized genome-wide effects of genetic variants in schizophrenia with significant predictive power. In a clinical sample of first-episode psychosis (FEP) patients, we estimated the ability of PRSs to discriminate case-control status and to predict the development of schizophrenia as opposed to other psychoses.

METHODS:

The sample (445 case and 265 control subjects) was genotyped on the Illumina HumanCore Exome BeadChip with an additional 828 control subjects of African ancestry genotyped on the Illumina Multi-Ethnic Genotyping Array. To calculate PRSs, we used the results from the latest Psychiatric Genomics Consortium schizophrenia meta-analysis. We examined the association of PRSs with case-control status and with schizophrenia versus other psychoses in European and African ancestry FEP patients and in a second sample of 248 case subjects with chronic psychosis.

RESULTS:

PRS had good discriminative ability of case-control status in FEP European ancestry individuals (9.4% of the variance explained, p < 10-6), but lower in individuals of African ancestry (R2 = 1.1%, p = .004). Furthermore, PRS distinguished European ancestry case subjects who went on to acquire a schizophrenia diagnosis from those who developed other psychotic disorders (R2 = 9.2%, p = .002).

CONCLUSIONS:

PRS was a powerful predictor of case-control status in a European sample of patients with FEP, even though a large proportion did not have an established diagnosis of schizophrenia at the time of assessment. PRS was significantly different between those case subjects who developed schizophrenia from those who did not, although the discriminative accuracy may not yet be sufficient for clinical utility in FEP.

KEYWORDS:

GWAS; Genetics; Polygenic score; Psychosis; Risk prediction; Schizophrenia

PMID:
27765268
DOI:
10.1016/j.biopsych.2016.06.028
[Indexed for MEDLINE]
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