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Variability in working memory performance explained by epistasis vs polygenic scores in the ZNF804A pathway

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Harvard

Schizophrenia Psychiatric Genome-wide Association Study (GWAS) Consortium & PGC schizophrenia working group (Thomas M Werge, Thomas Folkmann Hansen, members) 2014, 'Variability in working memory performance explained by epistasis vs polygenic scores in the ZNF804A pathway', JAMA Psychiatry, vol. 71, no. 7, pp. 778-85. https://doi.org/10.1001/jamapsychiatry.2014.528

APA

Schizophrenia Psychiatric Genome-wide Association Study (GWAS) Consortium, & PGC schizophrenia working group (Thomas M Werge, Thomas Folkmann Hansen, members) (2014). Variability in working memory performance explained by epistasis vs polygenic scores in the ZNF804A pathway. JAMA Psychiatry, 71(7), 778-85. https://doi.org/10.1001/jamapsychiatry.2014.528

CBE

Schizophrenia Psychiatric Genome-wide Association Study (GWAS) Consortium, PGC schizophrenia working group (Thomas M Werge, Thomas Folkmann Hansen, members) . 2014. Variability in working memory performance explained by epistasis vs polygenic scores in the ZNF804A pathway. JAMA Psychiatry. 71(7):778-85. https://doi.org/10.1001/jamapsychiatry.2014.528

MLA

Schizophrenia Psychiatric Genome-wide Association Study (GWAS) Consortium and PGC schizophrenia working group (Thomas M Werge, Thomas Folkmann Hansen, members) . "Variability in working memory performance explained by epistasis vs polygenic scores in the ZNF804A pathway". JAMA Psychiatry. 2014, 71(7). 778-85. https://doi.org/10.1001/jamapsychiatry.2014.528

Vancouver

Schizophrenia Psychiatric Genome-wide Association Study (GWAS) Consortium, PGC schizophrenia working group (Thomas M Werge, Thomas Folkmann Hansen, members) . Variability in working memory performance explained by epistasis vs polygenic scores in the ZNF804A pathway. JAMA Psychiatry. 2014 Jul 1;71(7):778-85. https://doi.org/10.1001/jamapsychiatry.2014.528

Author

Schizophrenia Psychiatric Genome-wide Association Study (GWAS) Consortium ; PGC schizophrenia working group (Thomas M Werge, Thomas Folkmann Hansen, members) . / Variability in working memory performance explained by epistasis vs polygenic scores in the ZNF804A pathway. In: JAMA Psychiatry. 2014 ; Vol. 71, No. 7. pp. 778-85.

Bibtex

@article{d82f9aa8a4c34d88992c3f85d71918f5,
title = "Variability in working memory performance explained by epistasis vs polygenic scores in the ZNF804A pathway",
abstract = "IMPORTANCE: We investigated the variation in neuropsychological function explained by risk alleles at the psychosis susceptibility gene ZNF804A and its interacting partners using single nucleotide polymorphisms (SNPs), polygenic scores, and epistatic analyses. Of particular importance was the relative contribution of the polygenic score vs epistasis in variation explained.OBJECTIVES: To (1) assess the association between SNPs in ZNF804A and the ZNF804A polygenic score with measures of cognition in cases with psychosis and (2) assess whether epistasis within the ZNF804A pathway could explain additional variation above and beyond that explained by the polygenic score.DESIGN, SETTING, AND PARTICIPANTS: Patients with psychosis (n = 424) were assessed in areas of cognitive ability impaired in schizophrenia including IQ, memory, attention, and social cognition. We used the Psychiatric GWAS Consortium 1 schizophrenia genome-wide association study to calculate a polygenic score based on identified risk variants within this genetic pathway. Cognitive measures significantly associated with the polygenic score were tested for an epistatic component using a training set (n = 170), which was used to develop linear regression models containing the polygenic score and 2-SNP interactions. The best-fitting models were tested for replication in 2 independent test sets of cases: (1) 170 individuals with schizophrenia or schizoaffective disorder and (2) 84 patients with broad psychosis (including bipolar disorder, major depressive disorder, and other psychosis).MAIN OUTCOMES AND MEASURES: Participants completed a neuropsychological assessment battery designed to target the cognitive deficits of schizophrenia including general cognitive function, episodic memory, working memory, attentional control, and social cognition.RESULTS: Higher polygenic scores were associated with poorer performance among patients on IQ, memory, and social cognition, explaining 1% to 3% of variation on these scores (range, P = .01 to .03). Using a narrow psychosis training set and independent test sets of narrow phenotype psychosis (schizophrenia and schizoaffective disorder), broad psychosis, and control participants (n = 89), the addition of 2 interaction terms containing 2 SNPs each increased the R2 for spatial working memory strategy in the independent psychosis test sets from 1.2% using the polygenic score only to 4.8% (P = .11 and .001, respectively) but did not explain additional variation in control participants.CONCLUSIONS AND RELEVANCE: These data support a role for the ZNF804A pathway in IQ, memory, and social cognition in cases. Furthermore, we showed that epistasis increases the variation explained above the contribution of the polygenic score.",
keywords = "Adult, Cognition Disorders, Epistasis, Genetic, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Male, Memory, Short-Term, Middle Aged, Multifactorial Inheritance, Neural Pathways, Neuropsychological Tests, Polymorphism, Single Nucleotide, Psychotic Disorders, Schizophrenia, Zinc Fingers",
author = "Nicodemus, {Kristin K} and April Hargreaves and Derek Morris and Richard Anney and Michael Gill and Aiden Corvin and Gary Donohoe and {Schizophrenia Psychiatric Genome-wide Association Study (GWAS) Consortium} and Wang, {August Gabriel} and {PGC schizophrenia working group (Thomas M Werge, Thomas Folkmann Hansen, members)} and Werge, {Thomas Mears} and Hansen, {Thomas Folkmann}",
year = "2014",
month = jul,
day = "1",
doi = "10.1001/jamapsychiatry.2014.528",
language = "English",
volume = "71",
pages = "778--85",
journal = "Archives of General Psychiatry",
issn = "2168-622X",
publisher = "American Medical Association",
number = "7",

}

RIS

TY - JOUR

T1 - Variability in working memory performance explained by epistasis vs polygenic scores in the ZNF804A pathway

AU - Nicodemus, Kristin K

AU - Hargreaves, April

AU - Morris, Derek

AU - Anney, Richard

AU - Gill, Michael

AU - Corvin, Aiden

AU - Donohoe, Gary

AU - Schizophrenia Psychiatric Genome-wide Association Study (GWAS) Consortium

AU - Wang, August Gabriel

AU - PGC schizophrenia working group (Thomas M Werge, Thomas Folkmann Hansen, members)

A2 - Werge, Thomas Mears

A2 - Hansen, Thomas Folkmann

PY - 2014/7/1

Y1 - 2014/7/1

N2 - IMPORTANCE: We investigated the variation in neuropsychological function explained by risk alleles at the psychosis susceptibility gene ZNF804A and its interacting partners using single nucleotide polymorphisms (SNPs), polygenic scores, and epistatic analyses. Of particular importance was the relative contribution of the polygenic score vs epistasis in variation explained.OBJECTIVES: To (1) assess the association between SNPs in ZNF804A and the ZNF804A polygenic score with measures of cognition in cases with psychosis and (2) assess whether epistasis within the ZNF804A pathway could explain additional variation above and beyond that explained by the polygenic score.DESIGN, SETTING, AND PARTICIPANTS: Patients with psychosis (n = 424) were assessed in areas of cognitive ability impaired in schizophrenia including IQ, memory, attention, and social cognition. We used the Psychiatric GWAS Consortium 1 schizophrenia genome-wide association study to calculate a polygenic score based on identified risk variants within this genetic pathway. Cognitive measures significantly associated with the polygenic score were tested for an epistatic component using a training set (n = 170), which was used to develop linear regression models containing the polygenic score and 2-SNP interactions. The best-fitting models were tested for replication in 2 independent test sets of cases: (1) 170 individuals with schizophrenia or schizoaffective disorder and (2) 84 patients with broad psychosis (including bipolar disorder, major depressive disorder, and other psychosis).MAIN OUTCOMES AND MEASURES: Participants completed a neuropsychological assessment battery designed to target the cognitive deficits of schizophrenia including general cognitive function, episodic memory, working memory, attentional control, and social cognition.RESULTS: Higher polygenic scores were associated with poorer performance among patients on IQ, memory, and social cognition, explaining 1% to 3% of variation on these scores (range, P = .01 to .03). Using a narrow psychosis training set and independent test sets of narrow phenotype psychosis (schizophrenia and schizoaffective disorder), broad psychosis, and control participants (n = 89), the addition of 2 interaction terms containing 2 SNPs each increased the R2 for spatial working memory strategy in the independent psychosis test sets from 1.2% using the polygenic score only to 4.8% (P = .11 and .001, respectively) but did not explain additional variation in control participants.CONCLUSIONS AND RELEVANCE: These data support a role for the ZNF804A pathway in IQ, memory, and social cognition in cases. Furthermore, we showed that epistasis increases the variation explained above the contribution of the polygenic score.

AB - IMPORTANCE: We investigated the variation in neuropsychological function explained by risk alleles at the psychosis susceptibility gene ZNF804A and its interacting partners using single nucleotide polymorphisms (SNPs), polygenic scores, and epistatic analyses. Of particular importance was the relative contribution of the polygenic score vs epistasis in variation explained.OBJECTIVES: To (1) assess the association between SNPs in ZNF804A and the ZNF804A polygenic score with measures of cognition in cases with psychosis and (2) assess whether epistasis within the ZNF804A pathway could explain additional variation above and beyond that explained by the polygenic score.DESIGN, SETTING, AND PARTICIPANTS: Patients with psychosis (n = 424) were assessed in areas of cognitive ability impaired in schizophrenia including IQ, memory, attention, and social cognition. We used the Psychiatric GWAS Consortium 1 schizophrenia genome-wide association study to calculate a polygenic score based on identified risk variants within this genetic pathway. Cognitive measures significantly associated with the polygenic score were tested for an epistatic component using a training set (n = 170), which was used to develop linear regression models containing the polygenic score and 2-SNP interactions. The best-fitting models were tested for replication in 2 independent test sets of cases: (1) 170 individuals with schizophrenia or schizoaffective disorder and (2) 84 patients with broad psychosis (including bipolar disorder, major depressive disorder, and other psychosis).MAIN OUTCOMES AND MEASURES: Participants completed a neuropsychological assessment battery designed to target the cognitive deficits of schizophrenia including general cognitive function, episodic memory, working memory, attentional control, and social cognition.RESULTS: Higher polygenic scores were associated with poorer performance among patients on IQ, memory, and social cognition, explaining 1% to 3% of variation on these scores (range, P = .01 to .03). Using a narrow psychosis training set and independent test sets of narrow phenotype psychosis (schizophrenia and schizoaffective disorder), broad psychosis, and control participants (n = 89), the addition of 2 interaction terms containing 2 SNPs each increased the R2 for spatial working memory strategy in the independent psychosis test sets from 1.2% using the polygenic score only to 4.8% (P = .11 and .001, respectively) but did not explain additional variation in control participants.CONCLUSIONS AND RELEVANCE: These data support a role for the ZNF804A pathway in IQ, memory, and social cognition in cases. Furthermore, we showed that epistasis increases the variation explained above the contribution of the polygenic score.

KW - Adult

KW - Cognition Disorders

KW - Epistasis, Genetic

KW - Female

KW - Genetic Predisposition to Disease

KW - Genetic Variation

KW - Genome-Wide Association Study

KW - Humans

KW - Male

KW - Memory, Short-Term

KW - Middle Aged

KW - Multifactorial Inheritance

KW - Neural Pathways

KW - Neuropsychological Tests

KW - Polymorphism, Single Nucleotide

KW - Psychotic Disorders

KW - Schizophrenia

KW - Zinc Fingers

U2 - 10.1001/jamapsychiatry.2014.528

DO - 10.1001/jamapsychiatry.2014.528

M3 - Journal article

C2 - 24828433

VL - 71

SP - 778

EP - 785

JO - Archives of General Psychiatry

JF - Archives of General Psychiatry

SN - 2168-622X

IS - 7

ER -

ID: 44522340