The UK Biobank imaging enhancement of 100,000 participants: rationale, data collection, management and future directions

Littlejohns, Thomas J.; Holliday, Joanne; Gibson, Lorna M; Garratt, Steve; Oesingmann, Niels; Alfaro-Almagro, Fidel; Bell, Jimmy D.; Boultwood, Chris; Collins, Rory; Conroy, Megan; Crabtree, Nicola; Doherty, Nicola; Frangi, Alejandro F.; Harvey, Nicholas C.; Leeson, Paul; Miller, Karla L.; Neubauer, Stefan; Petersen, Steffen E.; Sellors, Jonathan; Sheard, Simon; Smith, Stephen M.; Sudlow, Cathie; Matthews, Paul M.; Allen, Naomi E.

doi:10.1038/s41467-020-15948-9

Cited by 474 publications

(468 citation statements)

References 89 publications

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“…This process involves disruption of the psychological and biological systems mediating responses to stressful events and may remain difficult to describe in precise mechanistic terms until the culmination of large-scale longitudinal studies, such as the UK Biobank, the Avon Longitudinal Study of Parents and Children (ALSPAC), the Adolescent Brain Cognitive Development (ABCD) study and the IMAGEN project. [173][174][175][176] These are well placed to address the interactions of CT with biological markers (eg, genetic, brainderived, hormonal or inflammatory-based) to determine the contributions to the development of BD, its course and severity. Understanding the nature of and key players in this protracted course of causal events and the ensuing altered trajectories of individuals' mental wellbeing and resilience will be vital to the potential progress of effective monitoring, management and intervention standards.…”

Section: Discussionmentioning

confidence: 99%

<p>The Impact of Childhood Trauma on Developing Bipolar Disorder: Current Understanding and Ensuring Continued Progress</p>

Quidé¹,

Tozzi²,

Corcoran³

et al. 2020

NDT

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Childhood trauma (CT) has been repeatedly linked to earlier onset and greater severity of bipolar disorder (BD) in adulthood. However, such knowledge is mostly based on retrospective and cross-sectional studies in adults with BD. The first objective of this selective review is to characterize the short-term effects of CT in the development of BD by focusing on studies in young people. The second objective is to describe the longer-term consequences of CT by considering studies with adult participants. This review first outlines the most prominent hypotheses linking CT exposure and the onset of BD. Then, it summarizes the psychological and biological risk factors implicated in the development of BD, followed by a discussion of original studies that investigated the role of CT in young people with early-onset BD, youths at increased risk of developing BD, or young people with BD with a focus on subclinical and clinical outcome measures. The review considers additional biological and psychological factors associated with a negative impact of CT on the long-term course of BD in later adulthood. Finally, we discuss how the integration of information of CT can improve ongoing early identification of BD and mitigate severe clinical expression in later adulthood.

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Section: Discussionmentioning

confidence: 99%

<p>The Impact of Childhood Trauma on Developing Bipolar Disorder: Current Understanding and Ensuring Continued Progress</p>

Quidé¹,

Tozzi²,

Corcoran³

et al. 2020

NDT

View full text Add to dashboard Cite

show abstract

“…The UK Biobank is a prospective cohort study that enrolled 502,617 individuals aged 40-69 years of age from across the United Kingdom (Sudlow et al, 2015). As part of the study protocol, a subset of individuals underwent detailed imaging between years 2014 and 2019 including abdominal MRI (Littlejohns et al, 2020).…”

Section: Study Cohorts Uk Biobankmentioning

confidence: 99%

Machine learning enables new insights into clinical significance of and genetic contributions to liver fat accumulation

Haas

Friedman

Emdin

et al. 2020

Preprint

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Excess accumulation of liver fat - termed hepatic steatosis when fat accounts for > 5.5% of liver content - is a leading risk factor for end-stage liver disease and is strongly associated with important cardiometabolic disorders. Using a truth dataset of 4,511 UK Biobank participants with liver fat previously quantified via abdominal MRI imaging, we developed a machine learning algorithm to quantify liver fat with correlation coefficients of 0.97 and 0.99 in hold-out testing datasets and applied this algorithm to raw imaging data from an additional 32,192 participants. Among all 36,703 individuals with abdominal MRI imaging, median liver fat was 2.2%, with 6,250 (17%) meeting criteria for hepatic steatosis. Although individuals afflicted with hepatic steatosis were more likely to have been diagnosed with conditions such as obesity or diabetes, a prediction model based on clinical data alone without imaging could not reliably estimate liver fat content. To identify genetic drivers of variation in liver fat, we first conducted a common variant association study of 9.8 million variants, confirming three known associations for variants in the TM6SF2, APOE, and PNPLA3 genes and identifying five new variants associated with increased hepatic fat in or near the MARC1, ADH1B, TRIB1, GPAM and MAST3 genes. A polygenic score that integrated information from each of these eight variants was strongly associated with future clinical diagnosis of liver diseases. Next, we performed a rare variant association study in a subset of 11,021 participants with gene sequencing data available, identifying an association between inactivating variants in the APOB gene and substantially lower LDL cholesterol, but more than 10-fold increased risk of steatosis. Taken together, these results provide proof of principle for the use of machine learning algorithms on raw imaging data to enable epidemiologic studies and genetic discovery.

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“…This study used Magnetic Resonance Imaging (MRI) data from the UK-Biobank 15,61 . At the time of initiation of this study in the region of 40,000 individuals' data had been released.…”

Section: Methodsmentioning

confidence: 99%

Identifying genetic variants associated with cerebellar volume in 33,265 individuals from the UK-Biobank

Chambers

Escott‐Price

Legge

et al. 2020

Preprint

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There is expanding interest in researching the cerebellum given accumulating evidence of its important contributions to cognitive and emotional functions, in addition to more established sensorimotor roles. While large genome-wide association studies (GWAS) have shed light on the common allele architecture of cortical and subcortical brain structures, the cerebellum remains under investigated. We conducted a meta-GWAS of cerebellar volume in 33,265 UK-Biobank European participants. Results show cerebellar volume to be moderately heritable (h2SNP=50.6%). We identified 33 independent genome-wide associated SNPs with total cerebellar volume, with 6 of these SNPs mapped to protein-coding genes and 5 more shown to alter cerebellar gene expression. We highlight 21 unique candidate genes for follow-up analysis. Cerebellar volume showed significant genetic correlation with brainstem, pallidum and thalamus volumes, but no significant correlations with neuropsychiatric phenotypes. Our results provide important new knowledge of the genetic architecture of cerebellar volume and its relationship with other brain phenotypes.

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The UK Biobank imaging enhancement of 100,000 participants: rationale, data collection, management and future directions

Cited by 474 publications

References 89 publications

<p>The Impact of Childhood Trauma on Developing Bipolar Disorder: Current Understanding and Ensuring Continued Progress</p>

<p>The Impact of Childhood Trauma on Developing Bipolar Disorder: Current Understanding and Ensuring Continued Progress</p>

Machine learning enables new insights into clinical significance of and genetic contributions to liver fat accumulation

Identifying genetic variants associated with cerebellar volume in 33,265 individuals from the UK-Biobank

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