@article{f18f62c4c84d453bb33c724361fd9965,
title = "General and specific patterns of cortical gene expression as spatial correlates of complex cognitive functioning",
abstract = "Gene expression varies across the brain. This spatial patterning denotes specialised support for particular brain functions. However, the way that a given gene{\textquoteright}s expression fluctuates across the brain may be governed by general rules. Quantifying patterns of spatial covariation across genes would offer insights into the molecular characteristics of brain areas supporting, for example, complex cognitive functions. Here, we use principal component analysis to separate general and unique gene regulatory associations with cortical substrates of cognition. We find that the region-to-region variation in cortical expression profiles of 8235 genes covaries across two major principal components: gene ontology analysis suggests these dimensions are characterised by downregulation and upregulation of cell-signalling/modification and transcription factors. We validate these patterns out-of-sample and across different data processing choices. Brain regions more strongly implicated in general cognitive functioning (g; 3 cohorts, total meta-analytic N = 39,519) tend to be more balanced between downregulation and upregulation of both major components (indicated by regional component scores). We then identify a further 29 genes as candidate cortical spatial correlates of g, beyond the patterning of the two major components (|β| range = 0.18 to 0.53). Many of these genes have been previously associated with clinical neurodegenerative and psychiatric disorders, or with other health-related phenotypes. The results provide insights into the cortical organisation of gene expression and its association with individual differences in cognitive functioning.",
keywords = "gene expression, cognition, neuroanatomy, biological processes, meta-analysis, neurostructural correlations",
author = "Moodie, {Joanna E.} and Harris, {Sarah E.} and Harris, {Mathew A.} and Buchanan, {Colin R.} and Gail Davies and Adele Taylor and Paul Redmond and Liewald, {David C. M.} and {Vald{\'e}s Hern{\'a}ndez}, {Maria del C} and Susan Shenkin and Russ, {Tom C.} and {Mu{\~n}oz Maniega}, Susana and Michelle Luciano and Janie Corley and Aleks Stolicyn and Xueyi Shen and Douglas Steele and Gordon Waiter and Anca-Larisa Sandu and Bastin, {Mark E.} and Wardlaw, {Joanna M.} and Andrew McIntosh and Heather Whalley and Tucker-Drob, {Elliot M.} and Deary, {Ian J.} and Cox, {Simon R.}",
note = "Acknowledgements: We thank the participants of the three cohorts (UKB, Generation Scotland (STRADL) and LBC1936) for their participation and the research teams for their work in collecting, processing and giving access to these data for analysis. We are also thankful to the brain donors to the Allen Human Brain Atlas, BrainSpan Atlas and Human Brain Transcriptome Project, and to the people who collected and processed the data and made it openly available. SRC and JEM were supported by a Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society [221890/Z/20/Z]. For the purpose of open access, the author has applied a CC-BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The LBC1936, supported by the BBSRC & ESRC [BB/W008793/1] (which also supports SEH, SMM, JC, IJD and AT), Age UK [Disconnected Mind project], the Medical Research Council (MR/M01311/1; MR/K026992/1), the US National Institutes of Health [R01AG054628] and the University of Edinburgh. CRB, MEB, EMT-D, IJD and SRC were supported by a National Institutes of Health (NIH) research grant R01AG054628. TCR is a member of the Alzheimer Scotland Dementia Research Centre funded by Alzheimer Scotland. MCVH is funded by The Row Fogo Charitable Trust Centre for Research into Aging and the Brain (BRO-D.FID3668413). AS was funded as part of the STRADL study (Wellcome Trust reference 104036/Z/14/Z) and indirectly through the Lister Institute of Preventive Medicine research award for Prof. Daniel Smith (ref. 173096).",
year = "2024",
month = mar,
doi = "10.1002/hbm.26641",
language = "English",
volume = "45",
journal = "Human Brain Mapping",
issn = "1065-9471",
publisher = "Wiley-Liss Inc.",
number = "4",
}