- Title
- Evidence of genetic overlap and causal relationships between blood-based biochemical traits and human cortical anatomy
- Creator
- Kiltschewskij, Dylan J.; Reay, William R.; Cairns, Murray J.
- Relation
- NHMRC.1121474 https://purl.org/au-research/grants/nhmrc/1121474 & 1147644 http://purl.org/au-research/grants/nhmrc/1147644
- Relation
- Translational Psychiatry Vol. 12, Issue 1, no. 373
- Publisher Link
- http://dx.doi.org/10.1038/s41398-022-02141-3
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2022
- Description
- Psychiatric disorders such as schizophrenia are commonly associated with structural brain alterations affecting the cortex. Recent genetic evidence suggests circulating metabolites and other biochemical traits play a causal role in many psychiatric disorders which could be mediated by changes in the cerebral cortex. Here, we leveraged publicly available genome-wide association study data to explore shared genetic architecture and evidence for causal relationships between a panel of 50 biochemical traits and measures of cortical thickness and surface area. Linkage disequilibrium score regression identified 191 genetically correlated biochemical-cortical trait pairings, with consistent representation of blood cell counts and other biomarkers such as C-reactive protein (CRP), haemoglobin and calcium. Spatially organised patterns of genetic correlation were additionally uncovered upon clustering of region-specific correlation profiles. Interestingly, by employing latent causal variable models, we found strong evidence suggesting CRP and vitamin D exert causal effects on region-specific cortical thickness, with univariable and multivariable Mendelian randomization further supporting a negative causal relationship between serum CRP levels and thickness of the lingual region. Our findings suggest a subset of biochemical traits exhibit shared genetic architecture and potentially causal relationships with cortical structure in functionally distinct regions, which may contribute to alteration of cortical structure in psychiatric disorders.
- Subject
- psychiatric disorders; cortical thickness; brain; cerebral cortex
- Identifier
- http://hdl.handle.net/1959.13/1482602
- Identifier
- uon:50979
- Identifier
- ISSN:2158-3188
- Language
- eng
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