Thread by @ClaraMoreau9

✨✨We are thrilled to share 2 new papers published this week in:
#BiologicalPsychiatry: Genetic heterogeneity shapes brain connectivity in psychiatry
dx.doi.org/10.1016/j.biop…

#Brain: Brain connectivity mirrors genetic pleiotropy in psychiatric conditions academic.oup.com/brain/advance-…

1/7 #Polygenicity (=multiple genetic variants associated with one condition) and #pleiotropy (=one genetic variant influencing more than one trait) are key properties of the genomic architecture of #psychiatric conditions and represent major challenges in identifying mechanisms.

2/7 We processed 9 rs-fMRI datasets including 32,726 individuals, to examine the connectome-wide effects of 15 copy number variants, 7 polygenic scores (common variants), and 4 idiopathic psychiatric conditions (Autism, Schizophrenia, ADHD, Bipolar disorder).

3/7 #Pleiotropy, measured by genetic and transcriptomic correlations across pairs of conditions/traits, showed significant #concordance with connectomic correlations between the same pairs of conditions/traits. This suggests a causal genetic component for shared connectivity.

4/7 #Polygenicity: Effect sizes of CNVs on FC were correlated with their effects on cognitive ability. However, their effect sizes adjusted for the number of genes decreased from small oligogenic to large multigenic CNVs. Polygenic scores had disproportionately low effects on FC.

5/7 Multivariate analyses of genetic risks and psychiatric conditions showed convergence on the overconnectivity of the thalamus with the somatomotor network. This is in line with the fact that gross and fine motor skills are widely impaired in patients referred to NDD clinics.

6/7 I will conclude with our theoretical framework where genetic variants converge on a limited set of transcriptomic modules - leading to brain alterations (e.g., thalamomotor overconnectivity) that underly differences in cognitive/clinical dimensions observed #across diagnoses.

7/7 This #collaborative effort has been led by @JacquemontSeb @pierre_bellec @harvey_aa @kkumar_iitkgp + so many close collaborators @s_urchs @PTenigma @ThomasBourgeron @Winkytheelf @HuguetGuillaum5 (...) and has been feasible through the #open access to 🧠&🧬datasets!🙏🙏🙏