Biology subjects

Jude Gibson

Publications and source records attributed to Jude Gibson.

4 recordsLinked to original sources

bioRxiv2016

Association of polygenic risk for major psychiatric illness with subcortical volumes and white matter integrity in UK Biobank

Major depressive disorder (MDD), schizophrenia (SCZ) and bipolar disorder (BP) are common, disabling and heritable psychiatric diseases with a complex overlapping polygenic architecture. Individuals with these disorders, as well as their unaffected relatives, show widespread structural differences in corticostriatal and limbic networks. Structural variation in many of these brain regions is also heritable and polygenic but whether their genetic architecture overlaps with major psychiatric disorders is unknown. We sought to address this issue by examining the impact of polygenic risk of MDD, SCZ, and BP on subcortical brain volumes and white matter (WM) microstructure in a large single sample of neuroimaging data; the UK Biobank Imaging study. The first release of UK Biobank imaging data compromised participants with overlapping genetic data and subcortical volumes (N = 978) and WM measures (N = 816). Our, findings however, indicated no statistically significant associations between either subcortical volumes or WM microstructure, and polygenic risk for MDD, SCZ or BP. In the current study, we found little or no evidence for genetic overlap between major psychiatric disorders and structural brain measures. These findings suggest that subcortical brain volumes and WM microstructure may not be closely linked to the genetic mechanisms of major psychiatric disorders.

Neuroscience↗

bioRxiv2016

Do Regional Brain Volumes and Major Depressive Disorder Share Genetic Architecture: a study in Generation Scotland (n=19,762), UK Biobank (n=24,048) and the English Longitudinal Study of Ageing (n=5,766)

Major depressive disorder (MDD) is a heritable and highly debilitating condition. It is commonly associated with subcortical volumetric abnormalities, the most replicated of these being reduced hippocampal volume. Using the most recent published data from ENIGMA consortiums genome-wide association study (GWAS) of regional brain volume, we sought to test whether there is shared genetic architecture between 8 subcortical brain volumes and MDD. Using LD score regression utilising summary statistics from ENIGMA and the Psychiatric Genomics Consortium, we demonstrated that hippocampal volume was positively genetically correlated with MDD (rG=0.46, P=0.02), although this did not survive multiple comparison testing. None of other six brain regions studied were genetically correlated and amygdala volume heritability was too low for analysis. We also generated polygenic risk scores (PRS) to assess potential pleiotropy between regional brain volumes and MDD in three cohorts (Generation Scotland; Scottish Family Health Study (n=19,762), UK Biobank (n=24,048) and the English Longitudinal Study of Ageing (n=5,766). We used logistic regression to examine volumetric PRS and MDD and performed a meta-analysis across the three cohorts. No regional volumetric PRS demonstrated significant association with MDD or recurrent MDD. In this study we provide some evidence that hippocampal volume and MDD may share genetic architecture, albeit this did not survive multiple testing correction and was in the opposite direction to most reported phenotypic correlations. We therefore found no evidence to support a shared genetic architecture for MDD and regional subcortical volumes.

Genetics↗

bioRxiv2016

Dissection of Major Depressive Disorder using polygenic risk scores for Schizophrenia in two independent cohort.

Major depressive disorder (MDD) is known for its substantial clinical and suspected causal heterogeneity. It is characterised by low mood, psychomotor slowing, and increased levels of the personality trait neuroticism; factors which are also associated with schizophrenia (SCZ). It is possible that some cases of MDD may have a substantial genetic loading for SCZ. A sign of the presence of SCZ-like MDD sub-groups would be indicated by an interaction between MDD status and polygenic risk of SCZ on cognitive, personality and mood measures. In the current study, we hypothesised that higher SCZ-polygenic risk would define larger MDD case-control differences in cognitive ability, and smaller differences in distress and neuroticism. Polygenic risk scores (PGRS) for SCZ and their association with cognitive variables, neuroticism, mood, and psychological distress were estimated in a large population-based cohort (Generation Scotland: Scottish Family Health Study, GS:SFHS). Individuals were divided into those with, and without, depression (n=2587 & n=16,764 respectively) to test whether there was an interaction between MDD status and schizophrenia risk. Replication was sought in UK Biobank (n=33,525). In both GS:SFHS and UK Biobank we found significant interactions between SCZ-PGRS and MDD status for measures of psychological distress and neuroticism. In both cohorts there was a reduction of case-control differences on a background of higher genetic risk of SCZ. These findings suggest that depression on a background of high genetic risk for SCZ may show attenuated associations with distress and neuroticism. This may represent a causally distinct form of MDD more closely related to SCZ.

Neuroscience↗

bioRxiv2016

Genetic and environmental risk for chronic pain and the contribution of risk variants for psychiatric disorders. Results from Generation Scotland: Scottish Family Health Study and UK Biobank

BackgroundChronic pain is highly prevalent worldwide and a significant source of disability, yet its genetic and environmental risk factors are poorly understood. Its relationship with psychiatric illness, and major depressive disorder (MDD) in particular, is of particular importance. We sought to test the contribution of genetic factors and shared and unique environment to risk of chronic pain and its correlation with MDD in Generation Scotland: Scottish Family Health Study (GS:SFHS). We then sought to replicate any significant findings in the UK Biobank study.\n\nMethodsUsing family-based mixed-model analyses, we examined the contribution of genetics and environment to chronic pain using spouse, sibling and household groups as measures of shared environment. We then examined the correlation between chronic pain and MDD and estimated the contribution of genetic factors and shared environment. Finally, we used data from two independent genome-wide association studies to test whether chronic pain has a polygenic risk architecture and examine whether genomic risk of psychiatric disorder predicted chronic pain and whether genomic risk of chronic pain predicted MDD.\n\nResultsChronic pain is a moderately heritable trait (narrow sense heritability = 38.4%) which is more likely to be concordant in spouses and partners (variance explained 18.7%). Chronic pain is positively correlated with depression (rho = 0.13, p = 2.72x10-68) and it shows a tendency to cluster within families for genetic reasons (genetic correlation rho = 0.51, p = 8.24x10-19). Polygenic risk profiles for pain, generated using independent GWAS data, predicted chronic pain in both GS:SFHS (maximum {beta} = 6.18x10-2, p = 4.3x10-4) and UK Biobank (maximum {beta} = 5.68 x 10-2, p < 3x10-4). Genomic risk of MDD is also significantly associated with chronic pain in both GS:SFHS (maximum {beta} = 6.62x10-2, p = 4.3x10-4) and UK Biobank (maximum {beta} = 2.56x10-2, p < 3x10-4).\n\nConclusionsGenetic factors and chronic pain in a partner or spouse contribute substantially to the risk of chronic pain in the general population. Chronic pain is genetically correlated with MDD, has a polygenic architecture and is predicted by polygenic risk of MDD.

Genomics↗