|关键词||遗传和神经机制 精神疾病 影像遗传|
|英文摘要||Major psychiatric disorders, including attention deficit hyperactivity disorder, autism, bipolar disorder, major depression disorder and schizophrenia, are highly heritable and polygenic disorders. Evidence suggests that these five disorders have both shared and distinct genetic risks and neural mechanisms. The present work aims to help understand the neural and genetic mechanisms of these five major psychiatric disorders based on brain imaging and genomics.|
At first, the relationships between cross-disorder polygenic risk scores and polygenic risk scores for specific psychiatric disorders and functional connectivity were examined. 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.
In addition, the heritability of cortical surface area and gray matter volume of different regions in the brain was estimated. And the aim of this work was to find out whether there is a shared genetic basis of brain anatomy and these five psychiatric disorders. At first, the whole-genome heritability of 139 endophenotypes were estimated. And then the SNPs were divided into two sets with one sets including SNPs which were significantly associated with specific psychiatric disorders and then joint analysis was performed to estimate the heritability. Finally, permutation test was performed to test whether observed partial heritability is significantly higher than expectation. 23 of these 139 endophenotypes were found with significant heritability. But none of these partitioning of heritability showed a significantly enriched contribution of the sets including SNPs significantly associated with these five psychiatric disorders for brain phenotypes. The results may support that the brain anatomy is modulated by genetic factors and provide evidence that brain anatomy is a promising endophenotype for imaging genetics.
|王天奇. 基于基因组与脑影像的五种精神疾病遗传与神经机制研究[D]. 北京. 中国科学院大学,2017.|