TY - JOUR
T1 - A polygenic risk score analysis of psychosis endophenotypes across brain functional, structural, and cognitive domains
AU - Ranlund, Siri
AU - Calafato, Stella
AU - Thygesen, Johan H.
AU - Lin, Kuang
AU - Cahn, Wiepke
AU - Crespo-Facorro, Benedicto
AU - de Zwarte, Sonja M.C.
AU - Díez, Álvaro
AU - Di Forti, Marta
AU - Iyegbe, Conrad
AU - Jablensky, Assen
AU - Jones, Rebecca
AU - Hall, Mei Hua
AU - Kahn, Rene
AU - Kalaydjieva, Luba
AU - Kravariti, Eugenia
AU - Mcdonald, Colm
AU - Mcintosh, Andrew M.
AU - Mcquillin, Andrew
AU - Picchioni, Marco
AU - Prata, Diana P.
AU - Rujescu, Dan
AU - Schulze, Katja
AU - Shaikh, Madiha
AU - Toulopoulou, Timothea
AU - van Haren, Neeltje
AU - van Os, Jim
AU - Vassos, Evangelos
AU - Walshe, Muriel
AU - Lewis, Cathryn
AU - Murray, Robin M.
AU - Powell, John
AU - Bramon, Elvira
PY - 2017/8/29
Y1 - 2017/8/29
N2 - 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.
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.
KW - Bipolar disorder
KW - Cognition
KW - EEG
KW - Schizophrenia
KW - Single nucleotide polymorphism (SNP)
UR - http://www.scopus.com/inward/record.url?scp=85028537023&partnerID=8YFLogxK
U2 - 10.1002/ajmg.b.32581
DO - 10.1002/ajmg.b.32581
M3 - Article
AN - SCOPUS:85028537023
SN - 1552-4841
VL - 177
SP - 21
EP - 34
JO - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
IS - 1
ER -