TY - JOUR
T1 - Replicated evidence that endophenotypic expression of schizophrenia polygenic risk is greater in healthy siblings of patients compared to controls, suggesting gene-environment interaction. The EUGEI study
AU - van Os, Jim
AU - Pries, Lotta-Katrin
AU - Delespaul, Philippe
AU - Kenis, Gunter
AU - Luykx, Jurjen J
AU - Lin, Bochao D
AU - Richards, Alexander L
AU - Akdede, Berna
AU - Binbay, Tolga
AU - Altınyazar, Vesile
AU - Yalınçetin, Berna
AU - Gümüş-Akay, Güvem
AU - Cihan, Burçin
AU - Soygür, Haldun
AU - Ulaş, Halis
AU - Cankurtaran, Eylem Şahin
AU - Kaymak, Semra Ulusoy
AU - Mihaljevic, Marina M
AU - Petrovic, Sanja Andric
AU - Mirjanic, Tijana
AU - Bernardo, Miguel
AU - Cabrera, Bibiana
AU - Bobes, Julio
AU - Saiz, Pilar A
AU - García-Portilla, María Paz
AU - Sanjuan, Julio
AU - Aguilar, Eduardo J
AU - Santos, José Luis
AU - Jiménez-López, Estela
AU - Arrojo, Manuel
AU - Carracedo, Angel
AU - López, Gonzalo
AU - González-Peñas, Javier
AU - Parellada, Mara
AU - Maric, Nadja P
AU - Atbaşoğlu, Cem
AU - Ucok, Alp
AU - Alptekin, Köksal
AU - Saka, Meram Can
AU - Arango, Celso
AU - O'Donovan, Michael
AU - Rutten, Bart P F
AU - Guloksuz, Sinan
N1 - Funding Information:
Financial support. The European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EUGEI) Project is funded by grant agreement HEALTH-F2-2010-241909 (Project EUGEI) from the European Community’s Seventh Framework Programme. All the DNA samples from Turkey were provided by Ankara University Brain Research Center Biobank that was supported by AUBAPRO (10A6055003).
Publisher Copyright:
Copyright © Cambridge University Press 2019.
PY - 2020/8
Y1 - 2020/8
N2 - BACKGROUND: First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.METHODS: We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.RESULTS: In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.CONCLUSIONS: The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene-environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.
AB - BACKGROUND: First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.METHODS: We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.RESULTS: In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.CONCLUSIONS: The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene-environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.
KW - Cognition
KW - genetics
KW - schizophrenia
KW - schizotypy
UR - http://www.scopus.com/inward/record.url?scp=85070792804&partnerID=8YFLogxK
U2 - 10.1017/S003329171900196X
DO - 10.1017/S003329171900196X
M3 - Article
C2 - 31414981
SN - 0033-2917
VL - 50
SP - 1884
EP - 1897
JO - Psychological Medicine
JF - Psychological Medicine
IS - 11
ER -