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IMAGING GENETICS

From base pair to brain

Nature Neuroscience volume 24, pages 619–621 (2021)Cite this article

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In new research, Smith et al. identify thousands of novel genetic associations with human brain structure and function, including those on the X chromosome, by analyzing ~4,000 MRI-derived traits measured in almost 40,000 individuals from the UK Biobank resource.

Any two humans have, on average, about four million genetic differences, or variants, from each other. A well-defined subset leads to inter-individual differences in outwardly observable traits like height, weight, and eye color, but which lead to changes in traits more relevant to the neuroscience field? Our knowledge of genetic differences influencing human brain structure and function is expanding through the measurement of macroscale human brain traits using in vivo neuroimaging methods such as MRI in large, genotyped populations. The great hope for this field is that by finding genetic risk factors associated with both neuropsychiatric disorders and with brain structure and function, causal mechanisms will also be found leading from the genome through molecular and cellular sequelae to gross brain structural changes, altered behavior, and risk for neuropsychiatric disorders. In other words, imaging genetics may identify brain regions, functions, or traits causally involved in complicated, behaviorally defined neuropsychiatric disorders. With knowledge about which regions and/or functions are responsible for these disorders, genetic variant function can be modeled in appropriately differentiated stem cell model systems or within relevant brain regions of animal models to experimentally manipulate and potentially reverse disorder-associated pathways.

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Fig. 1: Overview of brain imaging GWAS in UK Biobank.

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Authors and Affiliations

  1. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Nana Matoba & Jason L. Stein

  2. UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Nana Matoba & Jason L. Stein

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  1. Nana Matoba
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  2. Jason L. Stein
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Correspondence to Jason L. Stein.

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The authors declare no competing interests.

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Matoba, N., Stein, J.L. From base pair to brain. Nat Neurosci 24, 619–621 (2021). https://doi.org/10.1038/s41593-021-00852-2

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