A multi-environments-gene interaction study of anxiety, depression and self-harm in the UK Biobank cohort

Abstract Background Wellbeing has a fundamental role in determining life expectancy and major depressive disorder (MDD) is one of the main modulating factors of wellbeing. This study evaluated the modulators of wellbeing in individuals with lifetime recurrent MDD (RMDD), single-episode MDD (SMDD) and no MDD in the UK Biobank. Methods Scores of happiness, meaningful life and satisfaction about functioning were condensed in a functioning-wellbeing score (FWS). We evaluated depression and anxiety characteristics, neuroticism-related traits, physical diseases, lifestyle and polygenic risk scores (PRSs) of psychiatric disorders. Other than individual predictors, we estimated the cumulative contribution to FWS of each group of predictors. We tested the indirect role of neuroticism on FWS through the modulation of depression manifestations using a mediation analysis. Results We identified 47 966, 21 117 and 207 423 individuals with lifetime RMDD, SMDD and no MDD, respectively. Depression symptoms and personality showed the largest impact on FWS (variance explained ~20%), particularly self-harm, worthlessness feelings during the worst depression, chronic depression, loneliness and neuroticism. Personality played a stronger role in SMDD. Anxiety characteristics showed a higher effect in SMDD and no MDD groups. Neuroticism played indirect effects through specific depressive symptoms that modulated FWS. Physical diseases and lifestyle explained only 4–5% of FWS variance. The PRS of MDD showed the largest effect on FWS compared to other PRSs. Conclusions This was the first study to comprehensively evaluate the predictors of wellbeing in relation to the history of MDD. The identified variables are important to identify individuals at risk and promote wellbeing.

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Intraocular pressure, glaucoma and dietary caffeine consumption: a gene–diet interaction study from the UK Biobank

Ophthalmology ◽

10.1016/j.ophtha.2020.12.009 ◽

2020 ◽

Author(s):

Jihye Kim ◽

Hugues Aschard ◽

Jae H. Kang ◽

Marleen AH. Lentjes ◽

Ron Do ◽

...

Keyword(s):

Intraocular Pressure ◽

Uk Biobank ◽

Interaction Study ◽

Caffeine Consumption ◽

The Uk

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Gene-Gene Interaction Detection with Deep Learning

10.1101/2021.03.12.435063 ◽

2021 ◽

Author(s):

Tianyu Cui ◽

Khaoula El Mekkaoui ◽

Jaakko Reinvall ◽

Aki S. Havulinna ◽

Pekka Marttinen ◽

...

Keyword(s):

Statistical Power ◽

Gene Interaction ◽

Uk Biobank ◽

New Approach ◽

Interaction Detection ◽

Complex Interactions ◽

Current Interaction ◽

The Uk ◽

Combine Information ◽

Hidden Nodes

ABSTRACTWe do not know the extent to which genetic interactions affect the observed phenotype in diseases, because the current interaction detection approaches are limited: they only consider interactions between the top SNPs of each gene, and only simple forms of interaction. We introduce methods for increasing the statistical power of interaction detection by taking into account all SNPs and complex interactions between them, beyond only the currently considered multiplicative relationships. In brief, the relation between SNPs and a phenotype is captured by a gene interaction neural network (NN), and the interactions are quantified by the Shapley score between hidden nodes, which are gene representations that optimally combine information from all SNPs in the gene. Additionally, we design a new permutation procedure tailored for NNs to assess the significance of interactions. The new approach outperformed existing alternatives on simulated datasets, and in a cholesterol study on the UK Biobank it detected six interactions which replicated on an independent FINRISK dataset, four of them novel findings.

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Associations of sleep phenotypes with severe intentional self-harm: a prospective analysis of the UK Biobank cohort

SLEEP ◽

10.1093/sleep/zsab053 ◽

2021 ◽

Author(s):

Binbin Lei ◽

Jihui Zhang ◽

Sijing Chen ◽

Jie Chen ◽

Lulu Yang ◽

...

Keyword(s):

Older Adults ◽

Mental Disorders ◽

Sleep Duration ◽

Uk Biobank ◽

Middle Aged ◽

Long Sleep ◽

Self Harm ◽

Future Risk ◽

The Uk

Abstract Study objectives We aimed to investigate the prospective associations of sleep phenotypes with severe intentional self-harm (ISH) in middle-aged and older adults. Methods A total of 499,159 participants (mean age: 56.55 ± 8.09 years; female: 54.4%) were recruited from the UK Biobank between 2006 and 2010 with follow-up until February 2016 in this population-based prospective study. Severe ISH was based on hospital inpatient records or a death cause of ICD-10 codes X60-X84. Patients with hospitalized diagnosis of severe ISH before the initial assessment were excluded. Sleep phenotypes, including sleep duration, chronotype, insomnia, sleepiness, and napping, were assessed at the initial assessments. Cox regression analysis was used to estimate temporal associations between sleep phenotypes and future risk of severe ISH. Results During a follow-up period of 7.04 years (SD: 0.88), 1,219 participants experienced the first hospitalization or death related to severe ISH. After adjusting for demographics, substance use, medical diseases, mental disorders, and other sleep phenotypes, short sleep duration (HR: 1.50, 95% CI: 1.23-1.83, P < .001), long sleep duration (HR: 1.56, 95% CI: 1.15-2.12, P = .004), and insomnia (usually: HR: 1.57, 95% CI: 1.31-1.89, P < .001) were significantly associated with severe ISH. Sensitivity analyses excluding participants with mental disorders preceding severe ISH yielded similar results. Conclusion The current study provides the empirical evidence of the independent prediction of sleep phenotypes, mainly insomnia, short and long sleep duration, for the future risk of severe ISH among middle-aged and older adults.

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Studying individual risk factors for self-harm in the UK Biobank: A polygenic scoring and Mendelian randomisation study

PLoS Medicine ◽

10.1371/journal.pmed.1003137 ◽

2020 ◽

Vol 17 (6) ◽

pp. e1003137 ◽

Cited By ~ 1

Author(s):

Kai Xiang Lim ◽

Frühling Rijsdijk ◽

Saskia P. Hagenaars ◽

Adam Socrates ◽

Shing Wan Choi ◽

...

Keyword(s):

Risk Factors ◽

Individual Risk ◽

Mendelian Randomisation ◽

Uk Biobank ◽

Self Harm ◽

The Uk ◽

Individual Risk Factors

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Living alone, loneliness and lack of emotional support as predictors of suicide and self-harm: seven-year follow up of the UK Biobank cohort

10.1101/19008458 ◽

2019 ◽

Author(s):

Richard J. Shaw ◽

Breda Cullen ◽

Nicholas Graham ◽

Donald M. Lyall ◽

Daniel Mackay ◽

...

Keyword(s):

Emotional Support ◽

Living Arrangements ◽

Hospital Admissions ◽

Cox Regression ◽

Living Alone ◽

Uk Biobank ◽

Self Harm ◽

The Uk ◽

The Relationship

AbstractBackgroundThe association between loneliness and suicide is complex, poorly understood, and there are no prior longitudinal studies. We aimed to investigate the relationship between living alone, loneliness and emotional support as predictors of death by suicide and self-harm.MethodsBetween 2006 and 2010 UK Biobank recruited over 0.5m people aged 37-73. This data was linked to prospective hospital admission and mortality records. Adjusted Cox regression models were used to investigate the relationship between self-reported measures of loneliness, emotional support and living arrangements and death by suicide and self-harm.ResultsFor women, there was no evidence that living arrangements, loneliness or lack of emotional support were associated with death by suicide. However, for men, both living alone (Hazard Ratio (HR) 2.19 95%CI 1.47-3.27) and with non-partners (HR 2.17 95%CI 1.28-3.69) were associated with death by suicide, independently of loneliness, which had a modest relationship with suicide in men (HR 1.45 95%CI 0.99-2.12). Associations between living alone and self-harm were explained by health for women, and by health, loneliness and emotional support for men. In fully adjusted models, loneliness was associated with hospital admissions for self-harm in both women (HR 1.90 95%CI 1.58-2.29) and men (HR 1.75 95%CI 1.41-2.18).ConclusionsFor men -but not for women- living alone or with a non-partner increased the risk of suicide, a finding not explained by loneliness. Loneliness may be more important as a risk factor for self-harm than for suicide, and appears to mitigate against any protective effect of cohabitation.

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Living alone, loneliness and lack of emotional support as predictors of suicide and self-harm: A nine-year follow up of the UK Biobank cohort

Journal of Affective Disorders ◽

10.1016/j.jad.2020.10.026 ◽

2021 ◽

Vol 279 ◽

pp. 316-323

Author(s):

Richard J. Shaw ◽

Breda Cullen ◽

Nicholas Graham ◽

Donald M. Lyall ◽

Daniel Mackay ◽

...

Keyword(s):

Emotional Support ◽

Living Alone ◽

Uk Biobank ◽

Self Harm ◽

The Uk

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Citrus‐Gene Interaction and Melanoma Risk in the UK Biobank

International Journal of Cancer ◽

10.1002/ijc.33862 ◽

2021 ◽

Author(s):

Andrew R. Marley ◽

Ming Li ◽

Victoria L. Champion ◽

Yiqing Song ◽

Jiali Han ◽

...

Keyword(s):

Gene Interaction ◽

Uk Biobank ◽

Melanoma Risk ◽

The Uk

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Ethnic Differences in Self-Poisoning Across South London

Crisis ◽

10.1027/0227-5910/a000258 ◽

2014 ◽

Vol 35 (4) ◽

pp. 268-272

Author(s):

Sean Cross ◽

Dinesh Bhugra ◽

Paul I. Dargan ◽

David M. Wood ◽

Shaun L. Greene ◽

...

Keyword(s):

Black Women ◽

Data Collection ◽

White Women ◽

Population Based ◽

Care Services ◽

Self Harm ◽

Managing Risk ◽

The Uk ◽

Incident Cases ◽

Minority Ethnic

Background: Self-poisoning (overdose) is the commonest form of self-harm cases presenting to acute secondary care services in the UK, where there has been limited investigation of self-harm in black and minority ethnic communities. London has the UK’s most ethnically diverse areas but presents challenges in resident-based data collection due to the large number of hospitals. Aims: To investigate the rates and characteristics of self-poisoning presentations in two central London boroughs. Method: All incident cases of self-poisoning presentations of residents of Lambeth and Southwark were identified over a 12-month period through comprehensive acute and mental health trust data collection systems at multiple hospitals. Analysis was done using STATA 12.1. Results: A rate of 121.4/100,000 was recorded across a population of more than half a million residents. Women exceeded men in all measured ethnic groups. Black women presented 1.5 times more than white women. Gender ratios within ethnicities were marked. Among those aged younger than 24 years, black women were almost 7 times more likely to present than black men were. Conclusion: Self-poisoning is the commonest form of self-harm presentation to UK hospitals but population-based rates are rare. These results have implications for formulating and managing risk in clinical services for both minority ethnic women and men.

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