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

Autor: Makowski C; Center for Multimodal Imaging and Genetics, University of California, San Diego, CA, USA., van der Meer D; Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands., Dong W; Department of Bioengineering, University of California, San Diego, CA, USA., Wang H; Center for Multimodal Imaging and Genetics, University of California, San Diego, CA, USA., Wu Y; Department of Bioengineering, University of California, San Diego, CA, USA., Zou J; Division of Biostatistics, Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, CA, USA., Liu C; Center for Multimodal Imaging and Genetics, University of California, San Diego, CA, USA., Rosenthal SB; Center for Computational Biology and Bioinformatics, University of California, San Diego, CA, USA., Hagler DJ Jr; Center for Multimodal Imaging and Genetics, University of California, San Diego, CA, USA., Fan CC; Center for Multimodal Imaging and Genetics, University of California, San Diego, CA, USA., Kremen WS; Department of Psychiatry and Center for Behavior Genetics of Aging, University of California, San Diego, CA, USA., Andreassen OA; Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Jernigan TL; Center for Human Development, University of California, San Diego, CA, USA., Dale AM; Center for Multimodal Imaging and Genetics, University of California, San Diego, CA, USA.; Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Zhang K; Department of Bioengineering, University of California, San Diego, CA, USA., Visscher PM; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia., Yang J; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.; School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China., Chen CH; Center for Multimodal Imaging and Genetics, University of California, San Diego, CA, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2022 Feb 04; Vol. 375 (6580), pp. 522-528. Date of Electronic Publication: 2022 Feb 03.
DOI: 10.1126/science.abe8457
Abstrakt: 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.
Databáze: MEDLINE
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