Phenotypic and genetic associations of quantitative magnetic susceptibility

Phenotypic and genetic associations of quantitative magnetic susceptibility in UK Biobank brain imaging

Chaoyue Wang, Aurea B. Martins-Bach, Fidel Alfaro-Almagro, Gwenaëlle Douaud, Johannes C. Klein, Alberto Llera, Cristiana Fiscone, Richard Bowtell, Lloyd T. Elliott, Stephen M. Smith, Benjamin C. Tendler & Karla L. Miller

Nature Neuroscience volume 25, pages 818–831 (2022)

A key aim in epidemiological neuroscience is identification of markers to assess brain health and monitor therapeutic interventions. Quantitative susceptibility mapping (QSM) is an emerging magnetic resonance imaging technique that measures tissue magnetic susceptibility and has been shown to detect pathological changes in tissue iron, myelin and calcification. We present an open resource of QSM-based imaging measures of multiple brain structures in 35,273 individuals from the UK Biobank prospective epidemiological study. We identify statistically significant associations of 251 phenotypes with magnetic susceptibility that include body iron, disease, diet and alcohol consumption. Genome-wide associations relate magnetic susceptibility to 76 replicating clusters of genetic variants with biological functions involving iron, calcium, myelin and extracellular matrix. These patterns of associations include relationships that are unique to QSM, in particular being complementary to T2* signal decay time measures. These new imaging phenotypes are being integrated into the core UK Biobank measures provided to researchers worldwide, creating the potential to discover new, non-invasive markers of brain health