Genome-wide association studies of brain imaging phenotypes in UK Biobank

By L. Elliott, Kevin Sharp, Fidel Alfaro-Almagro, Sinan Shi, Karla L. Miller, Gwenaëlle Douaud, Jonathan Marchini, Stephen M. Smith. 2018

738 citations recorded by the source corpus.

The genetic architecture of brain structure and function is largely unknown. To investigate this, we carried out genome-wide association studies of 3,144 functional and structural brain imaging phenotypes from UK Biobank (discovery dataset 8,428 subjects). Here we show that many of these phenotypes are heritable. We identify 148 clusters of associations between single nucleotide polymorphisms and imaging phenotypes that replicate at P < 0.05, when we would expect 21 to replicate by chance. Notable significant, interpretable associations include: iron transport and storage genes, related to magnetic susceptibility of subcortical brain tissue; extracellular matrix and epidermal growth factor genes, associated with white matter micro-structure and lesions; genes that regulate mid-line axon development, associated with organization of the pontine crossing tract; and overall 17 genes involved in development, pathway signalling and plasticity. Our results provide insights into the genetic architecture of the brain that are relevant to neurological and psychiatric disorders, brain development and ageing. Genome-wide association studies of brain imaging data from 8,428 individuals in UK Biobank show that many of the 3,144 traits studied are heritable, and genes associated with individual phenotypes are identified.

Subfields: Genetics, Radiology, Nuclear Medicine and Imaging

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Citations in the corpus

Brain age prediction using deep learning uncovers associated sequence variants (2019, positive): “Elliott et al. 52 suggest to use fMRI-derived head motion estimates to correct for confound effects due to head motion when running GWAS analysis on brain structure phenotypes.”
Neurodevelopment of the association cortices: Patterns, mechanisms, and implications for psychopathology (2021, neutral): “…of both brain structure (cortical thickness, surface area, sulcal width, intracortical myelination) and function (functional connectivity, signal amplitude) (Alexander-Bloch et al., 2020; Anderson et al., 2020a; Chen et al., 2011; Elliott et al., 2018; Schmitt et al., 2020; Valk et al., 2020).”
The genetic architecture of the human cerebral cortex (2020, background): “Of these 118 are novel, neither they nor their proxies have been associated with cortical SA or TH or volume in previous studies(12-14).”