Genetic association between Schizophrenia and Cortical Brain
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The amount of shared genetic variants between schizophrenia and cortical brain structure suggests overlapping molecular genetic mechanisms between cortical development and schizophrenia.

The objective was to investigate the extent of shared genetic architecture between schizophrenia and brain cortical surface area (SA) and thickness (TH) and to identify shared genomic loci.

Independent genome-wide association study data on schizophrenia and SA and TH were obtained. The extent of polygenic overlap was investigated using MiXeR. The specific shared genomic loci were identified by conditional/conjunctional false discovery rate analysis and were further examined in 3 independent cohorts.

- Based on genome-wide association study data from 139053 participants, MiXeR estimated schizophrenia to be more polygenic than total SA and average TH.

- Most SNVs associated with total SA and average TH may be associated with the development of schizophrenia.

- Subsequent conjunctional false discovery rate analysis identified 44 and 23 schizophrenia risk loci shared with total SA and average TH, respectively.

- The SNV associations of shared loci between schizophrenia and total SA revealed en masse concordant association between the discovery and independent cohorts.

- After removing high linkage disequilibrium regions, such as the major histocompatibility complex region, the shared loci were enriched in immunologic signature gene sets.

- Polygenic overlap and shared loci between schizophrenia and schizophrenia-associated regions of interest for SA (superior frontal and middle temporal gyri) and for TH (superior temporal, inferior temporal, and superior frontal gyri) were also identified.

This study demonstrated shared genetic loci between cortical morphometry and schizophrenia, among which a subset are associated with immunity.

JAMA Psychiatry
Source: https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2781372
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