Abstract
Multiple genetic variations impact on risk for schizophrenia. Recent analyses by the Psychiatric Genomics Consortium (PGC2) identified 128 SNPs genome-wide associated with the disorder. Furthermore, attention and working memory deficits are core features of schizophrenia, are heritable and have been associated with variation in glutamatergic neurotransmission. Based on this evidence, in a sample of healthy volunteers, we used SNPs associated with schizophrenia in PGC2 to construct a Polygenic-Risk-Score (PRS) reflecting the cumulative risk for schizophrenia, along with a Polygenic-Risk-Score including only SNPs related to genes implicated in glutamatergic signaling (Glu-PRS). We performed Factor Analysis for dimension reduction of indices of cognitive performance. Furthermore, both PRS and Glu-PRS were used as predictors of cognitive functioning in the domains of Attention, Speed of Processing and Working Memory. The association of the Glu-PRS on brain activity during the Variable Attention Control (VAC) task was also explored. Finally, in a second independent sample of healthy volunteers we sought to confirm the association between the Glu-PRS and both performance in the domain of Attention and brain activity during the VAC.We found that performance in Speed of Processing and Working Memory was not associated with any of the Polygenic-Risk-Scores. The Glu-PRS, but not the PRS was associated with Attention and brain activity during the VAC. The specific effects of Glu-PRS on Attention and brain activity during the VAC were also confirmed in the replication sample.Our results suggest a pathway specificity in the relationship between genetic risk for schizophrenia, the associated cognitive dysfunction and related brain processing.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 928-939 |
| Number of pages | 12 |
| Journal | European Neuropsychopharmacology |
| Volume | 27 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 1 2017 |
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Keywords
- Attention
- Cortex
- Glutamate
- Prefrontal
- Schizophrenia
- Working memory
ASJC Scopus subject areas
- Pharmacology
- Neurology
- Clinical Neurology
- Psychiatry and Mental health
- Biological Psychiatry
- Pharmacology (medical)
Cite this
A Polygenic Risk Score of glutamatergic SNPs associated with schizophrenia predicts attentional behavior and related brain activity in healthy humans. / Rampino, Antonio; Taurisano, Paolo; Fanelli, Giuseppe; Attrotto, Mariateresa; Torretta, Silvia; Antonucci, Linda Antonella; Miccolis, Grazia; Pergola, Giulio; Ursini, Gianluca; Maddalena, Giancarlo; Romano, Raffaella; Masellis, Rita; Di Carlo, Pasquale; Pignataro, Patrizia; Blasi, Giuseppe; Bertolino, Alessandro.
In: European Neuropsychopharmacology, Vol. 27, No. 9, 01.09.2017, p. 928-939.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A Polygenic Risk Score of glutamatergic SNPs associated with schizophrenia predicts attentional behavior and related brain activity in healthy humans
AU - Rampino, Antonio
AU - Taurisano, Paolo
AU - Fanelli, Giuseppe
AU - Attrotto, Mariateresa
AU - Torretta, Silvia
AU - Antonucci, Linda Antonella
AU - Miccolis, Grazia
AU - Pergola, Giulio
AU - Ursini, Gianluca
AU - Maddalena, Giancarlo
AU - Romano, Raffaella
AU - Masellis, Rita
AU - Di Carlo, Pasquale
AU - Pignataro, Patrizia
AU - Blasi, Giuseppe
AU - Bertolino, Alessandro
PY - 2017/9/1
Y1 - 2017/9/1
N2 - Multiple genetic variations impact on risk for schizophrenia. Recent analyses by the Psychiatric Genomics Consortium (PGC2) identified 128 SNPs genome-wide associated with the disorder. Furthermore, attention and working memory deficits are core features of schizophrenia, are heritable and have been associated with variation in glutamatergic neurotransmission. Based on this evidence, in a sample of healthy volunteers, we used SNPs associated with schizophrenia in PGC2 to construct a Polygenic-Risk-Score (PRS) reflecting the cumulative risk for schizophrenia, along with a Polygenic-Risk-Score including only SNPs related to genes implicated in glutamatergic signaling (Glu-PRS). We performed Factor Analysis for dimension reduction of indices of cognitive performance. Furthermore, both PRS and Glu-PRS were used as predictors of cognitive functioning in the domains of Attention, Speed of Processing and Working Memory. The association of the Glu-PRS on brain activity during the Variable Attention Control (VAC) task was also explored. Finally, in a second independent sample of healthy volunteers we sought to confirm the association between the Glu-PRS and both performance in the domain of Attention and brain activity during the VAC.We found that performance in Speed of Processing and Working Memory was not associated with any of the Polygenic-Risk-Scores. The Glu-PRS, but not the PRS was associated with Attention and brain activity during the VAC. The specific effects of Glu-PRS on Attention and brain activity during the VAC were also confirmed in the replication sample.Our results suggest a pathway specificity in the relationship between genetic risk for schizophrenia, the associated cognitive dysfunction and related brain processing.
AB - Multiple genetic variations impact on risk for schizophrenia. Recent analyses by the Psychiatric Genomics Consortium (PGC2) identified 128 SNPs genome-wide associated with the disorder. Furthermore, attention and working memory deficits are core features of schizophrenia, are heritable and have been associated with variation in glutamatergic neurotransmission. Based on this evidence, in a sample of healthy volunteers, we used SNPs associated with schizophrenia in PGC2 to construct a Polygenic-Risk-Score (PRS) reflecting the cumulative risk for schizophrenia, along with a Polygenic-Risk-Score including only SNPs related to genes implicated in glutamatergic signaling (Glu-PRS). We performed Factor Analysis for dimension reduction of indices of cognitive performance. Furthermore, both PRS and Glu-PRS were used as predictors of cognitive functioning in the domains of Attention, Speed of Processing and Working Memory. The association of the Glu-PRS on brain activity during the Variable Attention Control (VAC) task was also explored. Finally, in a second independent sample of healthy volunteers we sought to confirm the association between the Glu-PRS and both performance in the domain of Attention and brain activity during the VAC.We found that performance in Speed of Processing and Working Memory was not associated with any of the Polygenic-Risk-Scores. The Glu-PRS, but not the PRS was associated with Attention and brain activity during the VAC. The specific effects of Glu-PRS on Attention and brain activity during the VAC were also confirmed in the replication sample.Our results suggest a pathway specificity in the relationship between genetic risk for schizophrenia, the associated cognitive dysfunction and related brain processing.
KW - Attention
KW - Cortex
KW - Glutamate
KW - Prefrontal
KW - Schizophrenia
KW - Working memory
UR - http://www.scopus.com/inward/record.url?scp=85021241209&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85021241209&partnerID=8YFLogxK
U2 - 10.1016/j.euroneuro.2017.06.005
DO - 10.1016/j.euroneuro.2017.06.005
M3 - Article
C2 - 28651857
AN - SCOPUS:85021241209
VL - 27
SP - 928
EP - 939
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
SN - 0924-977X
IS - 9
ER -