title: Polygenic risk for five psychiatric disorders and cross-disorder and disorder-specific neural connectivity in two independent populations.
abstract: Major psychiatric disorders, including attention deficit hyperactivity disorder (ADHD), autism (AUT), bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SZ), are highly heritable and polygenic. Evidence suggests that these five disorders have both shared and distinct genetic risks and neural connectivity abnormalities. To measure aggregate genetic risks, the polygenic risk score (PGRS) was computed. Two independent general populations (N = 360 and N = 323) were separately examined to investigate whether the cross-disorder PGRS and PGRS for a specific disorder were associated with individual variability in functional connectivity. Consistent altered functional connectivity was found with the bilateral insula: for the left supplementary motor area and the left superior temporal gyrus with the cross-disorder PGRS, for the left insula and right middle and superior temporal lobe associated with the PGRS for autism, for the bilateral midbrain, posterior cingulate, cuneus, and precuneus associated with the PGRS for BD, and for the left angular gyrus and the left dorsolateral prefrontal cortex associated with the PGRS for schizophrenia. No significant functional connectivity was found associated with the PGRS for ADHD and MDD. Our findings indicated that genetic effects on the cross-disorder and disorder-specific neural connectivity of common genetic risk loci are detectable in the general population. Our findings also indicated that polygenic risk contributes to the main neurobiological phenotypes of psychiatric disorders and that identifying cross-disorder and specific functional connectivity related to polygenic risks may elucidate the neural pathways for these disorders.
authors.affiliation: Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Tianqi
authors.initials: T
authors.lastname: Wang
authors.affiliation: Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.affiliation: Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Meifang
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Qin
authors.affiliation: Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Chunshui
authors.initials: C
authors.lastname: Yu
authors.affiliation: Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, 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, QLD 4072, Australia; Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China.
authors.forename: Tianzi
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; Center for Excellence in Brain Science and Intelligence Technology, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity; D001321:Autistic Disorder; D001714:Bipolar Disorder; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000000981:diagnostic imaging*; D066264:Datasets as Topic; D003865:Major Depressive Disorder; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D001523:Mental Disorders / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics; D020412:Multifactorial Inheritance / Q000235:genetics; D010100:Oxygen / Q000097:blood; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: Cross-disorder; Disorder-specific; Neural connectivity; Polygenic risk score; fMRI