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Neuroimage Clin. 2017 Feb 13;14:441-449. doi: 10.1016/j.nicl.2017.02.011. eCollection 2017.

Polygenic risk for five psychiatric disorders and cross-disorder and disorder-specific neural connectivity in two independent populations.

Author information

1
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.
2
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.
3
Department of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China.
4
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.
5
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.

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.

KEYWORDS:

Cross-disorder; Disorder-specific; Neural connectivity; Polygenic risk score; fMRI

PMID:
28275544
PMCID:
PMC5328751
DOI:
10.1016/j.nicl.2017.02.011
[Indexed for MEDLINE]
Free PMC Article

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