(11/11) Also for anyone who may be curious about exploring sulcal complexity, feel free to check out our previous containerized toolkit to derive it from FreeSurfer outputs! figshare.com/articles/cod...
(10/11) ++ Christopher Ching, Joan Han, Nancy Lee, @jmulle.bsky.social , Sarah Shultz, Sébastien Jacquemont, @carriebearden.bsky.social !
(9/11) Very grateful to my wonderful mentors (Petra Vértes, Ed Bullmore, @bogglerapture.bsky.social) and amazing full team that made this work possible!!! ( @rshaf.bsky.social , Siyuan Liu, Elizabeth Levitis, Kuaikuai Duan, @kkumar.bsky.social, Charles Schleifer, Rune Boen, continued!..)
(8/11) Together, we nominate new and largely separable pathways of genetic influence on cortical folding, either by disrupting canalized neurodevelopmental programs for sulcation (rare variation) or by exerting distributed, pleiotropic influences on the developing cortical sheet (common variation)
(7/11) Annotating these genes' fetal expression, we found that sulcal complexity genes are enriched for distinct cellular and molecular developmental processes that span the entire radial axis of the fetal brain - suggesting no one tissue or cell type can be isolated in a model of cortical folding
(6/11) Our GWAS of sulcal complexity for each of 40 sulci across the cortex identified strong associations at specific loci and many candidate genes regulating sulcal complexity (50 in expanded set), with many genes implicated in fetal developmental processes that co-occur with sulcal formation
(5/11) Interestingly, these gradients align with a previous hypothesis that sharp gradients in arealization/cytoarchitecture may predispose locations for buckling or folding of the cortex during the rapid expansion of the fetal brain in the 2nd trimester
(4/11) We next examined common genetic variation in the UK Biobank. SNP-based heritability of sulcal complexity was not associated with above patterns of rare variation, but had striking alignment with cortical surface area -- with gradients of genetic correlations that "flip" sign across sulci
(3/11) These rare variant effects on sulcal complexity reveal a unique neurodevelopmental signal not linked to area/thickness but instead converging on a spatial axis linked to the timing of prenatal sulcation. Rare variants seem to contract/expand how differentiated linear vs complex sulci present
(2/11) First, across 9 diverse neurogenetic syndrome cohorts, we identified moderate-to-large effects (|standardized effect|>0.4) on sulcal complexity for many (14%) sulci, revealing visible changes in morphology -- such as atypical interruptions in the left STS for individuals with 16p11.2 deletion
(🧵1/11) We derived sulcal complexity -- a measure rooted in fetal sulcation, scoring folds from linear to complex shape -- in large cohorts with rare (n=615, 9 syndromes) and common (n~29,000, UKB) genetic variation, enabling us to systematically compare the genetic influences from each
How may rare vs. common genetic variation separately influence how our brains – and their complex folding patterns – take shape? 🧬 🧠
Check out our new preprint (and final work from my PhD!) out now! ( + thread below) www.biorxiv.org/content/10.6...