Impact of Polygenic Risk for Schizophrenia on Cortical Structure in UK Biobank.
Birth weight
Cortical surface area
Cortical thickness
Cortical volume
Polygenic risk
Schizophrenia
Journal
Biological psychiatry
ISSN: 1873-2402
Titre abrégé: Biol Psychiatry
Pays: United States
ID NLM: 0213264
Informations de publication
Date de publication:
01 10 2019
01 10 2019
Historique:
received:
03
10
2018
revised:
05
04
2019
accepted:
05
04
2019
pubmed:
7
6
2019
medline:
2
7
2020
entrez:
8
6
2019
Statut:
ppublish
Résumé
Schizophrenia is a neurodevelopmental disorder with many genetic variants of individually small effect contributing to phenotypic variation. Lower cortical thickness (CT), surface area, and cortical volume have been demonstrated in people with schizophrenia. Furthermore, a range of obstetric complications (e.g., lower birth weight) are consistently associated with an increased risk for schizophrenia. We investigated whether a high polygenic risk score for schizophrenia (PGRS-SCZ) is associated with CT, surface area, and cortical volume in UK Biobank, a population-based sample, and tested for interactions with birth weight. Data were available for 2864 participants (n We found a significant negative association between PGRS-SCZ and global CT; a higher PGRS-SCZ was associated with lower CT across the whole brain. We also report a significant negative association between PGRS-SCZ and insular lobe CT. PGRS-SCZ was not associated with birth weight and no PGRS-SCZ × birth weight interactions were found. These results suggest that individual differences in CT are partly influenced by genetic variants and are most likely not due to factors downstream of disease onset. This approach may help to elucidate the genetic pathophysiology of schizophrenia. Further investigation in case-control and high-risk samples could help identify any localized effects of PGRS-SCZ, and other potential schizophrenia risk factors, on CT as symptoms develop.
Sections du résumé
BACKGROUND
Schizophrenia is a neurodevelopmental disorder with many genetic variants of individually small effect contributing to phenotypic variation. Lower cortical thickness (CT), surface area, and cortical volume have been demonstrated in people with schizophrenia. Furthermore, a range of obstetric complications (e.g., lower birth weight) are consistently associated with an increased risk for schizophrenia. We investigated whether a high polygenic risk score for schizophrenia (PGRS-SCZ) is associated with CT, surface area, and cortical volume in UK Biobank, a population-based sample, and tested for interactions with birth weight.
METHODS
Data were available for 2864 participants (n
RESULTS
We found a significant negative association between PGRS-SCZ and global CT; a higher PGRS-SCZ was associated with lower CT across the whole brain. We also report a significant negative association between PGRS-SCZ and insular lobe CT. PGRS-SCZ was not associated with birth weight and no PGRS-SCZ × birth weight interactions were found.
CONCLUSIONS
These results suggest that individual differences in CT are partly influenced by genetic variants and are most likely not due to factors downstream of disease onset. This approach may help to elucidate the genetic pathophysiology of schizophrenia. Further investigation in case-control and high-risk samples could help identify any localized effects of PGRS-SCZ, and other potential schizophrenia risk factors, on CT as symptoms develop.
Identifiants
pubmed: 31171358
pii: S0006-3223(19)31283-1
doi: 10.1016/j.biopsych.2019.04.013
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
536-544Subventions
Organisme : Medical Research Council
ID : MR/K026992/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 213674/Z/18/Z
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019. Published by Elsevier Inc.