Discovery of genomic loci of the human cerebral cortex using genetically informed brain atlases

Carolina Makowski, Dennis van der Meer, Weixiu Dong, Hao Wang, Yan Wu, Jingjing Zou, Cin Liu, Sara B Rosenthal, Donald J Hagler, Chun Chieh Fan, William S Kremen, Ole A Andreassen, Terry L Jernigan, Anders M Dale, Kun Zhang, Peter M Visscher, Jian Yang, Chi-Hua Chen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article numberA27
Pages (from-to)522-528
Number of pages7
JournalScience
Volume375
Issue number6580
DOIs
Publication statusPublished - 4 Feb 2022

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Cerebral Cortex/anatomy & histology
  • Child
  • Chromatin/genetics
  • 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/genetics
  • Middle Aged
  • Molecular Sequence Annotation
  • Multifactorial Inheritance
  • Polymorphism, Single Nucleotide
  • Regulatory Sequences, Nucleic Acid
  • SINGLE-CELL
  • ELEMENTS
  • FUNCTIONAL IMPACT
  • ANNOTATION
  • RISK
  • HERITABILITY
  • SEGMENTATION
  • POPULATION-STRUCTURE
  • WIDE ASSOCIATION
  • COMPLEX TRAITS

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