Genetic influences on cognitive endophenotypes in schizophrenia

Ronald A Yeo; Steven W Gangestad; Esther Walton; Stefan Ehrlich; Jessica Pommy; Jessica A Turner; Jingyu Liu; Andrew R Mayer; S Charles Schulz; Beng-Choon Ho; Juan R Bustillo; Thomas H Wassink; Scott R Sponheim; Eric M Morrow; Vince D Calhoun

doi:10.1016/j.schres.2014.03.022

Genetic influences on cognitive endophenotypes in schizophrenia

Ronald A Yeo, Steven W Gangestad, Esther Walton, Stefan Ehrlich, Jessica Pommy, Jessica A Turner, Jingyu Liu, Andrew R Mayer, S Charles Schulz, Beng-Choon Ho, Juan R Bustillo, Thomas H Wassink, Scott R Sponheim, Eric M Morrow, Vince D Calhoun

Bristol Medical School (PHS)

Research output: Contribution to journal › Article (Academic Journal) › peer-review

14 Citations (Scopus)

Abstract

BACKGROUND: Cognitive deficits are prominent in schizophrenia and represent promising endophenotypes for genetic research.

METHODS: The current study investigated the importance of two conceptually distinct genetic aggregates, one based on copy number variations (uncommon deletion burden), and one based on single nucleotide polymorphisms identified in recent risk studies (genetic risk score). The impact of these genetic factors, and their interaction, was examined on cognitive endophenotypes defined by principal component analysis (PCA) in a multi-center sample of 50 patients with schizophrenia and 86 controls. PCA was used to identify three different types of executive function (EF: planning, fluency, and inhibition), and in separate analyses, a measure general cognitive ability (GCA).

RESULTS: Cognitive deficits were prominent among individuals with schizophrenia, but no group differences were evident for either genetic factor. Among patients the deletion burden measures predicted cognitive deficits across the three EF components and GCA. Further, an interaction was noted between the two genetic factors for both EF and GCA and the observed patterns of interaction suggested antagonistic epistasis. In general, the set of genetic interactions examined predicted a substantial portion of variance in these cognitive endophenotypes.

LIMITATIONS: Though adequately powered, our sample size is small for a genetic study.

CONCLUSIONS: These results draw attention to genetic interactions and the possibility that genetic influences on cognition differ in patients and controls.

Original language	English
Pages (from-to)	71-5
Number of pages	5
Journal	Schizophrenia Research
Volume	156
Issue number	1
DOIs	https://doi.org/10.1016/j.schres.2014.03.022
Publication status	Published - Jun 2014

Keywords

Adult
Analysis of Variance
Cognition Disorders
Endophenotypes
Female
Follow-Up Studies
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Male
Neuropsychological Tests
Principal Component Analysis
Psychiatric Status Rating Scales
Schizophrenia
Young Adult

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title = "Genetic influences on cognitive endophenotypes in schizophrenia",

abstract = "BACKGROUND: Cognitive deficits are prominent in schizophrenia and represent promising endophenotypes for genetic research.METHODS: The current study investigated the importance of two conceptually distinct genetic aggregates, one based on copy number variations (uncommon deletion burden), and one based on single nucleotide polymorphisms identified in recent risk studies (genetic risk score). The impact of these genetic factors, and their interaction, was examined on cognitive endophenotypes defined by principal component analysis (PCA) in a multi-center sample of 50 patients with schizophrenia and 86 controls. PCA was used to identify three different types of executive function (EF: planning, fluency, and inhibition), and in separate analyses, a measure general cognitive ability (GCA).RESULTS: Cognitive deficits were prominent among individuals with schizophrenia, but no group differences were evident for either genetic factor. Among patients the deletion burden measures predicted cognitive deficits across the three EF components and GCA. Further, an interaction was noted between the two genetic factors for both EF and GCA and the observed patterns of interaction suggested antagonistic epistasis. In general, the set of genetic interactions examined predicted a substantial portion of variance in these cognitive endophenotypes.LIMITATIONS: Though adequately powered, our sample size is small for a genetic study.CONCLUSIONS: These results draw attention to genetic interactions and the possibility that genetic influences on cognition differ in patients and controls.",

keywords = "Adult, Analysis of Variance, Cognition Disorders, Endophenotypes, Female, Follow-Up Studies, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Male, Neuropsychological Tests, Principal Component Analysis, Psychiatric Status Rating Scales, Schizophrenia, Young Adult",

author = "Yeo, {Ronald A} and Gangestad, {Steven W} and Esther Walton and Stefan Ehrlich and Jessica Pommy and Turner, {Jessica A} and Jingyu Liu and Mayer, {Andrew R} and Schulz, {S Charles} and Beng-Choon Ho and Bustillo, {Juan R} and Wassink, {Thomas H} and Sponheim, {Scott R} and Morrow, {Eric M} and Calhoun, {Vince D}",

year = "2014",

month = jun,

doi = "10.1016/j.schres.2014.03.022",

language = "English",

volume = "156",

pages = "71--5",

journal = "Schizophrenia Research",

issn = "0920-9964",

publisher = "Elsevier",

number = "1",

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T1 - Genetic influences on cognitive endophenotypes in schizophrenia

AU - Yeo, Ronald A

AU - Gangestad, Steven W

AU - Walton, Esther

AU - Ehrlich, Stefan

AU - Pommy, Jessica

AU - Turner, Jessica A

AU - Liu, Jingyu

AU - Mayer, Andrew R

AU - Schulz, S Charles

AU - Ho, Beng-Choon

AU - Bustillo, Juan R

AU - Wassink, Thomas H

AU - Sponheim, Scott R

AU - Morrow, Eric M

AU - Calhoun, Vince D

PY - 2014/6

Y1 - 2014/6

N2 - BACKGROUND: Cognitive deficits are prominent in schizophrenia and represent promising endophenotypes for genetic research.METHODS: The current study investigated the importance of two conceptually distinct genetic aggregates, one based on copy number variations (uncommon deletion burden), and one based on single nucleotide polymorphisms identified in recent risk studies (genetic risk score). The impact of these genetic factors, and their interaction, was examined on cognitive endophenotypes defined by principal component analysis (PCA) in a multi-center sample of 50 patients with schizophrenia and 86 controls. PCA was used to identify three different types of executive function (EF: planning, fluency, and inhibition), and in separate analyses, a measure general cognitive ability (GCA).RESULTS: Cognitive deficits were prominent among individuals with schizophrenia, but no group differences were evident for either genetic factor. Among patients the deletion burden measures predicted cognitive deficits across the three EF components and GCA. Further, an interaction was noted between the two genetic factors for both EF and GCA and the observed patterns of interaction suggested antagonistic epistasis. In general, the set of genetic interactions examined predicted a substantial portion of variance in these cognitive endophenotypes.LIMITATIONS: Though adequately powered, our sample size is small for a genetic study.CONCLUSIONS: These results draw attention to genetic interactions and the possibility that genetic influences on cognition differ in patients and controls.

AB - BACKGROUND: Cognitive deficits are prominent in schizophrenia and represent promising endophenotypes for genetic research.METHODS: The current study investigated the importance of two conceptually distinct genetic aggregates, one based on copy number variations (uncommon deletion burden), and one based on single nucleotide polymorphisms identified in recent risk studies (genetic risk score). The impact of these genetic factors, and their interaction, was examined on cognitive endophenotypes defined by principal component analysis (PCA) in a multi-center sample of 50 patients with schizophrenia and 86 controls. PCA was used to identify three different types of executive function (EF: planning, fluency, and inhibition), and in separate analyses, a measure general cognitive ability (GCA).RESULTS: Cognitive deficits were prominent among individuals with schizophrenia, but no group differences were evident for either genetic factor. Among patients the deletion burden measures predicted cognitive deficits across the three EF components and GCA. Further, an interaction was noted between the two genetic factors for both EF and GCA and the observed patterns of interaction suggested antagonistic epistasis. In general, the set of genetic interactions examined predicted a substantial portion of variance in these cognitive endophenotypes.LIMITATIONS: Though adequately powered, our sample size is small for a genetic study.CONCLUSIONS: These results draw attention to genetic interactions and the possibility that genetic influences on cognition differ in patients and controls.

KW - Adult

KW - Analysis of Variance

KW - Cognition Disorders

KW - Endophenotypes

KW - Female

KW - Follow-Up Studies

KW - Genetic Association Studies

KW - Genetic Predisposition to Disease

KW - Humans

KW - Male

KW - Neuropsychological Tests

KW - Principal Component Analysis

KW - Psychiatric Status Rating Scales

KW - Schizophrenia

KW - Young Adult

U2 - 10.1016/j.schres.2014.03.022

DO - 10.1016/j.schres.2014.03.022

M3 - Article (Academic Journal)

C2 - 24768440

SN - 0920-9964

VL - 156

SP - 71

EP - 75

JO - Schizophrenia Research

JF - Schizophrenia Research

IS - 1

ER -

Genetic influences on cognitive endophenotypes in schizophrenia

Abstract

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