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Schizophr Bull. 2017 May 1;43(3):673-680. doi: 10.1093/schbul/sbw051.

Polygenic Risk for Schizophrenia Influences Cortical Gyrification in 2 Independent General Populations.

Liu B1,2, Zhang X1,2, Cui Y1,2, Qin W3, Tao Y1,2, Li J1,2, Yu C3, Jiang T1,2,4,5,6.

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Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
Department of Radiology, Tianjin Medical University General Hospital, Tianjin, China.
Center for Excellence in Brain Science and Intelligence Technology, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
Queensland Brain Institute, The University of Queensland, Brisbane, Australia.
Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.


Schizophrenia is highly heritable, whereas the effect of each genetic variant is very weak. Since clinical heterogeneity and complexity of schizophrenia is high, considerable effort has been made to relate genetic variants to underlying neurobiological aspects of schizophrenia (endophenotypes). Given the polygenic nature of schizophrenia, our goal was to form a measure of additive genetic risk and explore its relationship to cortical morphology. Utilizing the data from a recent genome-wide association study that included nearly 37 000 cases of schizophrenia, we computed a polygenic risk score (PGRS) for each subject in 2 independent and healthy general populations. We then investigated the effect of polygenic risk for schizophrenia on cortical gyrification calculated from 3.0T structural imaging data in the discovery dataset (N = 315) and replication dataset (N = 357). We found a consistent effect of the polygenic risk for schizophrenia on cortical gyrification in the inferior parietal lobules in 2 independent general-population samples. A higher PGRS was significantly associated with a lower local gyrification index in the bilateral inferior parietal lobles, where case-control differences have been reported in previous studies on schizophrenia. Our findings strongly support the effectiveness of both PGRSs and endophenotypes in establishing the genetic architecture of psychiatry. Our findings may provide some implications regarding individual differences in the genetic risk for schizophrenia to cortical morphology and brain development.


cortical gyrification; inferior parietal lobule; polygenic risk score; schizophrenia

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