“General Dimensions of Human Brain Morphometry Inferred from Genome-Wide Association Data”, 2021-10-25 (; backlinks; similar):
The human brain is organised into networks of interconnected regions that have highly correlated volumes. In this study, we aim to triangulate insights into brain organization and its relationship with cognitive ability and ageing, by analysing genetic data.
We estimated general genetic dimensions of human brain morphometry within the whole brain, and 9 predefined canonical brain networks of interest. We did so based on principal components analysis (PCA) of genetic correlations among grey-matter volumes for 83 cortical and subcortical regions (nparticipants = 36,778).
We found that the corresponding general dimension of brain morphometry accounts for 40% of the genetic variance in the individual brain regions across the whole brain, and 47–65% within each network of interest. This genetic correlation structure of regional brain morphometry closely resembled the phenotypic correlation structure of the same regions. Applying a novel multivariate methodology for calculating SNP effects for each of the general dimensions identified, we find that general genetic dimensions of morphometry within networks are negatively associated with brain age (rg = −0.34) and profiles characteristic of age-related neurodegeneration, as indexed by cross-sectional age-volume correlations (r = −0.27). The same genetic dimensions were positively associated with a genetic general factor of cognitive ability (rg = 0.17–0.21 for different networks).
We have provided a statistical framework to index general dimensions of shared genetic morphometry that vary between brain networks, and report evidence for a shared biological basis underlying brain morphometry, cognitive ability, and brain ageing, that are underpinned by general genetic factors.
…This indicates that the genetic association between brain morphometry and cognitive ability was not driven by specific network configurations. Instead, dimensions of shared genetic morphometry in general indexed genetic variance relevant to larger brain volumes and a brain organization that is advantageous for better cognitive performance. This was regardless of how many brain regions and from which regions the measure of shared genetic morphometry was extracted. This lack of differentiation between networks, in how strongly they correlate with cognitive ability, is in line with the suggestion that the total number of neurons in the mammalian cortex, which should at least partly correspond to its volume, is a major predictor of higher cognitive ability.37 These findings suggest that highly shared brain morphometry between regions, and its genetic analogue, indicate a generally bigger, and cognitively better-functioning brain.