The Course of Illness After Initial Diagnosis of Major Depression

Shelton, Richard C.

doi:10.1001/jamapsychiatry.2015.3457

Cited by 6 publications

(4 citation statements)

References 6 publications

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“…Major Depression is phenotypically correlated with many traits including several behavioural measures, brain structure and function, specific cognitive functions, and several physical conditions 8–13 . It is important to investigate the associations between the genetic predisposition to Major Depression and a wide range of phenotypes, to help identify causal risk factors, risk-conferring mechanisms and the causal consequences of Major Depression 14 .…”

Section: Introductionmentioning

confidence: 99%

A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

Shen

Howard

Adams

et al. 2019

Preprint

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AbstractDepression is the leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Depression is known to be heritable with a polygenic architecture, and results from genome-wide associations studies are providing summary statistics with increasing polygenic signal that can be used to estimate genetic risk scores for prediction in independent samples. This provides a timely opportunity to identify traits that are associated with polygenic risk of depression in the large and consistently phenotyped UK Biobank sample. Using the Psychiatric Genomics Consortium (PGC), 23andMe and non-imaging UK Biobank datasets as reference samples, we estimated polygenic risk scores for depression (depression-PRS) in a discovery sample of 10,674 people and a replication sample of 11,214 people from the UK Biobank Imaging Study, testing for associations with 210 behavioural and 278 neuroimaging phenotypes. In the discovery sample, 93 traits were significantly associated with depression-PRS after multiple testing correction. Among these, 92 traits were in the same direction, and 69 were significant in the replication analysis. For imaging traits that replicated across samples, higher depression-PRS was associated with lower global white matter microstructure, association-fibre and thalamic-radiation microstructural integrity (absolute β: 0.023 to 0.040, PFDR: 0.045 to 3.92×10-4). Mendelian Randomisation analysis showed a causal effect of liability to depression on these structural brain measures (β: 0.125 to 0.707, pFDR<0.048). Replicated behavioural traits that positively associated with depression-PRS included sleep problems, smoking status, measures of pain and stressful life experiences, and those negatively associated with depression-PRS included subjective ratings of physical health (absolute β: 0.014 to 0.180, PFDR: 0.046 to 8.54×10-15). Effect of depression PRS on mental health in the presence of reported childhood trauma, stressful life events and those living in more socially deprived areas showed increased variance explained by 1.42 – 4.08 times (pFDR for their interaction with depression-PRS: 0.049 to 0.003). Overall, the present study revealed replicable associations between depression-PRS and white matter microstructure that appeared to be a causal consequence of liability to depression. Analyses provided further evidence that greater effects of polygenic risk of depression are found in individuals exposed to risk-conferring environments.

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Section: Introductionmentioning

confidence: 99%

A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

Shen

Howard

Adams

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Major depression is phenotypically correlated with many behaviours, brain structure and function measures, cognitive domains and physical conditions [8][9][10][11][12][13] . It is important to investigate the associations between the genetic predisposition to major depression and these phenotypes, to help identify shared causal risk factors, mechanisms and the causal consequences of major depression 14 .…”

mentioning

confidence: 99%

A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

et al. 2020

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Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery (N = 10,674) and replication (N = 11,214) imaging sample from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure (β: 0.125 to 0.868, p FDR < 0.043). Several behavioural traits are also associated with depression-PRS (β: 0.014 to 0.180, p FDR : 0.049 to 1.28 × 10 −14) and we find a significant and positive interaction between depression-PRS and adverse environmental exposures on mental health outcomes. This study reveals replicable associations between depression-PRS and white matter microstructure. Our results indicate that white matter microstructure differences may be a causal consequence of liability to depression.

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“…5, Supplementary Data 6 and 7 and Supplementary Figs. [7][8][9][10][11]. The neuroimaging phenotypes include (β and p FDR reported for significant effects): global gMD (gMD-Total; β: 0.125-0.724, p FDR for MR: 0.041-0.022, significant for all three MR methods), gMD in thalamic radiations…”

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

52 a Phenome-Wide Association and Mendelian Randomisation Study of Polygenic Risk for Depression in Uk Biobank

Shen

Howard

Adams

et al. 2019

European Neuropsychopharmacology

View full text Add to dashboard Cite

Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery (N = 10,674) and replication (N = 11,214) imaging sample from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure (β: 0.125 to 0.868, p FDR < 0.043). Several behavioural traits are also associated with depression-PRS (β: 0.014 to 0.180, p FDR : 0.049 to 1.28 × 10 −14 ) and we find a significant and positive interaction between depression-PRS and adverse environmental exposures on mental health outcomes. This study reveals replicable associations between depression-PRS and white matter microstructure. Our results indicate that white matter microstructure differences may be a causal consequence of liability to depression.

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The Course of Illness After Initial Diagnosis of Major Depression

Cited by 6 publications

References 6 publications

A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

52 a Phenome-Wide Association and Mendelian Randomisation Study of Polygenic Risk for Depression in Uk Biobank

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