|Title||Discovery of genomic loci of the human cerebral cortex using genetically informed brain atlases.|
|Publication Type||Journal Article|
|Year of Publication||2022|
|Authors||Makowski C, van der Meer D, Dong W, Wang H, Wu Y, Zou J, Liu C, Rosenthal SB, Hagler DJ, Fan CChieh, Kremen WS, Andreassen OA, Jernigan TL, Dale AM, Zhang K, Visscher PM, Yang J, Chen C-H|
|Date Published||2022 02 04|
|Keywords||Adult, Aged, Aged, 80 and over, Cerebral Cortex, Child, Chromatin, Cohort Studies, Female, Gene Ontology, Genetic Association Studies, Genetic Loci, Genetic Variation, Genome, Human, Genome-Wide Association Study, Humans, Magnetic Resonance Imaging, Male, Mental Disorders, Middle Aged, Molecular Sequence Annotation, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Regulatory Sequences, Nucleic Acid|
To determine the impact of genetic variants on the brain, we used genetically informed brain atlases in genome-wide association studies of regional cortical surface area and thickness in 39,898 adults and 9136 children. We uncovered 440 genome-wide significant loci in the discovery cohort and 800 from a post hoc combined meta-analysis. Loci in adulthood were largely captured in childhood, showing signatures of negative selection, and were linked to early neurodevelopment and pathways associated with neuropsychiatric risk. Opposing gradations of decreased surface area and increased thickness were associated with common inversion polymorphisms. Inferior frontal regions, encompassing Broca's area, which is important for speech, were enriched for human-specific genomic elements. Thus, a mixed genetic landscape of conserved and human-specific features is concordant with brain hierarchy and morphogenetic gradients.
|Grant List||R01 MH118281 / MH / NIMH NIH HHS / United States |
/ / CIHR / Canada
R56 AG061163 / AG / NIA NIH HHS / United States
R01 MH122688 / MH / NIMH NIH HHS / United States
R01 AG022381 / AG / NIA NIH HHS / United States
R01 AG050595 / AG / NIA NIH HHS / United States
Discovery of genomic loci of the human cerebral cortex using genetically informed brain atlases.