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
Tarih
2020Yazar
Richards, Alexander L.
Akdede, Berna
Binbay, Tolga
ALTINYAZAR, VESİLE
Yalincetin, Berna
GÜMÜŞ-AKAY, GÜVEM
Cihan, Burcin
Soyguer, Haldun
ULAŞ, HALİS
Cankurtaran, Eylem Sahin
Kaymak, Semra Ulusoy
Mihaljevic, Marina M.
Petrovic, Sanja Andric
Mirjanic, Tijana
Arrojo, Manuel
Carracedo, Angel
Lopez, Gonzalo
Gonzalez-Penas, Javier
Parellada, Mara
Maric, Nadja P.
Atbasoglu, Cem
Ucok, Alp
ALPTEKİN, KÖKSAL
SAKA, MERAM CAN
Arango, Celso
O'Donovan, Michael
Rutten, Bart P. F.
Guloksuz, Sinan
Lin, Bochao D.
Luykx, Jurjen J.
Kenis, Gunter
Delespaul, Philippe
Pries, Lotta-Katrin
van Os, Jim
Jimenez-Lopez, Estela
Santos, Jose Luis
Aguilar, Eduardo J.
Sanjuan, Julio
Garcia-Portilla, Maria Paz
Saiz, Pilar A.
Bobes, Julio
Cabrera, Bibiana
Bernardo, Miguel
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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.
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