RT info:eu-repo/semantics/article
T1 A polygenic risk score analysis of psychosis endophenotypes across brain functional, structural, and cognitive domains
A1 Ranlund, Siri
A1 Calafato, Stella
A1 Thygesen, Johan H.
A1 Lin, Kuang
A1 Cahn, Wiepke
A1 Crespo‐Facorro, Benedicto
A1 de Zwarte, Sonja M.C.
A1 Díez, Álvaro
A1 Di Forti, Marta
A1 Iyegbe, Conrad
A1 Jablensky, Assen
A1 Jones, Rebecca
A1 Hall, Mei‐Hua
A1 Kahn, Rene
A1 Kalaydjieva, Luba
A1 Kravariti, Eugenia
A1 McDonald, Colm
A1 McIntosh, Andrew M.
A1 McQuillin, Andrew
A1 Picchioni, Marco
A1 Prata, Diana P.
A1 Rujescu, Dan
A1 Schulze, Katja
A1 Shaikh, Madiha
A1 Toulopoulou, Timothea
A1 van Haren, Neeltje
A1 van Os, Jim
A1 Vassos, Evangelos
A1 Walshe, Muriel
A1 Lewis, Cathryn
A1 Murray, Robin M.
A1 Powell, John
A1 Bramon, Elvira
AB This large multi-center study investigates the relationships between genetic risk for schizophrenia and bipolar disorder, and multi-modal endophenotypes for psychosis. The sample included 4,242 individuals; 1,087 patients with psychosis, 822 unaffected first-degree relatives of patients, and 2,333 controls. Endophenotypes included the P300 event-related potential (N = 515), lateral ventricular volume (N = 798), and the cognitive measures block design (N = 3,089), digit span (N = 1,437), and the Ray Auditory Verbal Learning Task (N = 2,406). Data were collected across 11 sites in Europe and Australia; all genotyping and genetic analyses were done at the same laboratory in the United Kingdom. We calculated polygenic risk scores for schizophrenia and bipolar disorder separately, and used linear regression to test whether polygenic scores influenced the endophenotypes. Results showed that higher polygenic scores for schizophrenia were associated with poorer performance on the block design task and explained 0.2% (p = 0.009) of the variance. Associations in the same direction were found for bipolar disorder scores, but this was not statistically significant at the 1% level (p = 0.02). The schizophrenia score explained 0.4% of variance in lateral ventricular volumes, the largest across all phenotypes examined, although this was not significant (p = 0.063). None of the remaining associations reached significance after correction for multiple testing (with alpha at 1%). These results indicate that common genetic variants associated with schizophrenia predict performance in spatial visualization, providing additional evidence that this measure is an endophenotype for the disorder with shared genetic risk variants. The use of endophenotypes such as this will help to characterize the effects of common genetic variation in psychosis.
SN 1552-4841
YR 2017
FD 2017
LK https://uvadoc.uva.es/handle/10324/66447
UL https://uvadoc.uva.es/handle/10324/66447
LA spa
NO American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 177(1), 21-34
DS UVaDOC
RD 11-jul-2024