Polygenic risk score contribution to psychosis prediction in a target population of persons at clinical high risk Article Swipe

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D.O. Perkins , L.O. Loohuis , J. Barbee , J. Ford , Clark Jeffries , J. Addington , C.E. Bearden , K.S. Cadenhead , T.D. Cannon , B.A. Cornblatt , D.H. Mathalon , T.H. McGlashan , L.J. Seidman , M. Tsuang , E.F. Walker , S.W. Woods ·

YOU? · · 2020 · Open Access · · DOI: https://doi.org/10.17615/htz9-8344

Objective: The 2-year risk of psychosis in persons who meet research criteria for a high-risk syndrome is about 15%225%; improvements in risk prediction accuracy would benefit the development and implementation of preventive interventions. The authors sought to assess polygenic risk score (PRS) prediction of subsequent psychosis in persons at high risk and to determine the impact of adding the PRS to a previously validated psychosis risk calculator. Methods: Persons meeting research criteria for psychosis high risk (N=764) and unaffected individuals (N=279) were followed for up to 2 years. The PRS was based on the latest schizophrenia and bipolar genome-wide association studies. Variables in the psychosis risk calculator included stressful life events, trauma, disordered thought content, verbal learning, information processing speed, and family history of psychosis. Results: For Europeans, the PRS varied significantly by group and was higher in the psychosis converter group compared with both the nonconverter and unaffected groups, but was similar for the nonconverter group compared with the unaffected group. For non-Europeans, the PRS varied significantly by group; the difference between the converters and nonconverters was not significant, but the PRS was significantly higher in converters than in unaffected individuals, and it did not differ between nonconverters and unaffected individuals. The R2liability (R2 adjusted for the rate of disease risk in the population being studied, here assuming a 2-year psychosis risk between 10% and 30%) for Europeans varied between 9.2% and 12.3% and for non-Europeans between 3.5% and 4.8%. The amount of risk prediction information contributed by the addition of the PRS to the risk calculator was less than severity of disordered thoughts and similar to or greater than for other variables. For Europeans, the PRS was correlated with risk calculator variables of information processing speed and verbal memory. Conclusions: The PRS discriminates psychosis converters from nonconverters and modestly improves individualized psychosis risk prediction when added to a psychosis risk calculator. The schizophrenia PRS shows promise in enhancing risk prediction in persons at high risk for psychosis, although its potential utility is limited by poor performance in persons of non-European ancestry.

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Polygenic risk score Psychosis Population Psychology Clinical psychology Medicine Psychiatry Biology Genetics Environmental health Single-nucleotide polymorphism Gene Genotype

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Type: article
Language: en
Landing Page: https://doi.org/10.17615/htz9-8344
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Title: Polygenic risk score contribution to psychosis prediction in a target population of persons at clinical high risk

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Language: en

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Publication year: 2020

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Publication date: 2020-01-01

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Authors: D.O. Perkins, L.O. Loohuis, J. Barbee, J. Ford, Clark Jeffries, J. Addington, C.E. Bearden, K.S. Cadenhead, T.D. Cannon, B.A. Cornblatt, D.H. Mathalon, T.H. McGlashan, L.J. Seidman, M. Tsuang, E.F. Walker, S.W. Woods

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Concepts: Polygenic risk score, Psychosis, Population, Psychology, Clinical psychology, Medicine, Psychiatry, Biology, Genetics, Environmental health, Single-nucleotide polymorphism, Gene, Genotype

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abstract_inverted_index.studies.	100
abstract_inverted_index.syndrome	15
abstract_inverted_index.thoughts	264
abstract_inverted_index.Europeans	228
abstract_inverted_index.Variables	101
abstract_inverted_index.ancestry.	342
abstract_inverted_index.converter	140
abstract_inverted_index.determine	53
abstract_inverted_index.enhancing	319
abstract_inverted_index.high-risk	14
abstract_inverted_index.learning,	116
abstract_inverted_index.polygenic	38
abstract_inverted_index.potential	331
abstract_inverted_index.psychosis	5, 45, 64, 73, 104, 139, 221, 295, 303, 310
abstract_inverted_index.stressful	108
abstract_inverted_index.validated	63
abstract_inverted_index.variables	283
abstract_inverted_index.Europeans,	127, 275
abstract_inverted_index.Objective:	0
abstract_inverted_index.calculator	106, 257, 282
abstract_inverted_index.converters	174, 187, 296
abstract_inverted_index.correlated	279
abstract_inverted_index.difference	171
abstract_inverted_index.disordered	112, 263
abstract_inverted_index.population	214
abstract_inverted_index.prediction	22, 42, 245, 305, 321
abstract_inverted_index.preventive	31
abstract_inverted_index.previously	62
abstract_inverted_index.processing	118, 286
abstract_inverted_index.psychosis,	328
abstract_inverted_index.psychosis.	124
abstract_inverted_index.subsequent	44
abstract_inverted_index.unaffected	78, 148, 160, 190, 200
abstract_inverted_index.variables.	273
abstract_inverted_index.R2liability	203
abstract_inverted_index.association	99
abstract_inverted_index.calculator.	66, 312
abstract_inverted_index.contributed	247
abstract_inverted_index.development	27
abstract_inverted_index.genome-wide	98
abstract_inverted_index.individuals	79
abstract_inverted_index.information	117, 246, 285
abstract_inverted_index.performance	337
abstract_inverted_index.Conclusions:	291
abstract_inverted_index.improvements	19
abstract_inverted_index.individuals,	191
abstract_inverted_index.individuals.	201
abstract_inverted_index.non-European	341
abstract_inverted_index.nonconverter	146, 155
abstract_inverted_index.significant,	179
abstract_inverted_index.discriminates	294
abstract_inverted_index.non-Europeans	236
abstract_inverted_index.nonconverters	176, 198, 298
abstract_inverted_index.schizophrenia	95, 314
abstract_inverted_index.significantly	131, 167, 184
abstract_inverted_index.implementation	29
abstract_inverted_index.individualized	302
abstract_inverted_index.interventions.	32
abstract_inverted_index.non-Europeans,	163
cited_by_percentile_year
countries_distinct_count	1
institutions_distinct_count	16
citation_normalized_percentile.value	0.33474919
citation_normalized_percentile.is_in_top_1_percent	False
citation_normalized_percentile.is_in_top_10_percent	False