Comment on the Relationship Between Common Variant Schizophrenia Liability and Number of Offspring in the UK Biobank

ABSTRACTINTRODUCTIONThe association between visual impairment (VI) and the risk of dementia has been poorly understood. We sought to investigate the VI-dementia relationship in the UK Biobank Study.METHODSA total of 117,187 volunteers (aged 40-69 years) deemed free of dementia at baseline were included. Habitual distance visual acuity worse than 0.3 logMAR units in the better-seeing eye was used to define VI. The incident dementia was based on electronically linked hospital inpatient and death records.RESULTSDuring a median follow up of 5.96 years, the presence of VI was significantly associated with incident dementia (HR=1.78, 95% CI: 1.18-2.68, P=0.006). There was a clear trend between the severity of VI and the risk of dementia (P for trend=0.002).DISCUSSIONVisually impaired individuals were more likely to develop incident dementia, with a progressively greater risk among those with worse visual acuity. Our findings highlight the value of regular vision screening and elimination of VI.HIGHLIGHTSThe association between VI and dementia has been poorly understood;VI is associated with incident dementia in non-demented adults;There is a clear trend between the severity of VI and the risk of dementia;VI may be a marker of increased dementia risk.RESEARCH IN CONTEXTSYSTEMATIC REVIEWWe searched and reviewed the literature using traditional sources (e.g., PubMed and GoogleScholar). While the association between VI and cognitive function/decline are increasingly studies, investigation of the association between VI and the risk of dementia has been largely overlooked.INTERPRETATIONWe found that visually impaired individuals were more likely to develop incident dementia, with a progressively greater risk among those with worse visual acuity. Our findings imply that VI may be an important marker of dementia.FUTURE DIRECTIONSThese findings call for more studies to investigate (a) the role of visual acuity changes on the risk of dementia; (b) the relationship between other components of visual function and incident dementia; (c) the relationship between eye diseases and incident dementia; and (d) the potential benefits of vision rehabilitation on dementia prevention.

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The relationship between obesity and neuropsychiatric disorders based on the UK Biobank disease-network map

10.26226/morressier.5785edc8d462b80296c996af ◽

2016 ◽

Author(s):

Gabriella Juhasz

Keyword(s):

Neuropsychiatric Disorders ◽

Uk Biobank ◽

Disease Network ◽

The Uk ◽

The Relationship

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The relationship between obesity and neuropsychiatric disorders based on the UK Biobank disease-network map

European Neuropsychopharmacology ◽

10.1016/s0924-977x(16)31279-2 ◽

2016 ◽

Vol 26 ◽

pp. S349-S350

Author(s):

G. Juhasz ◽

P. Marx ◽

G. Hullam ◽

P. Antal ◽

G. Bagdy ◽

...

Keyword(s):

Neuropsychiatric Disorders ◽

Uk Biobank ◽

Disease Network ◽

The Uk ◽

The Relationship

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Population-based neuroimaging reveals traces of childbirth in the maternal brain

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1910666116 ◽

2019 ◽

Vol 116 (44) ◽

pp. 22341-22346 ◽

Cited By ~ 14

Author(s):

Ann-Marie G. de Lange ◽

Tobias Kaufmann ◽

Dennis van der Meer ◽

Luigi A. Maglanoc ◽

Dag Alnæs ◽

...

Keyword(s):

Brain Aging ◽

Population Based ◽

Uk Biobank ◽

Long Term Effects ◽

Pregnancy And Postpartum ◽

Maternal Brain ◽

The Uk ◽

Prospective Longitudinal ◽

The Relationship

Maternal brain adaptations have been found across pregnancy and postpartum, but little is known about the long-term effects of parity on the maternal brain. Using neuroimaging and machine learning, we investigated structural brain characteristics in 12,021 middle-aged women from the UK Biobank, demonstrating that parous women showed less evidence of brain aging compared to their nulliparous peers. The relationship between childbirths and a “younger-looking” brain could not be explained by common genetic variation or relevant confounders. Although prospective longitudinal studies are needed, the results suggest that parity may involve neural changes that could influence women’s brain aging later in life.

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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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Obesity impairs cognitive function via metabolic syndrome and cerebrovascular disease: an SEM analysis in 15,000 adults from the UK Biobank

10.1101/2020.06.26.174086 ◽

2020 ◽

Cited By ~ 2

Author(s):

Filip Morys ◽

Mahsa Dadar ◽

Alain Dagher

Keyword(s):

Metabolic Syndrome ◽

Cognitive Impairment ◽

White Matter ◽

Cerebrovascular Disease ◽

Cortical Thickness ◽

White Matter Hyperintensities ◽

Uk Biobank ◽

Central Nervous System Damage ◽

The Uk ◽

The Relationship

AbstractChronic obesity is associated with several complications, including cognitive impairment and dementia. However, we have piecemeal knowledge of the mechanisms linking obesity to central nervous system damage. Adiposity leads to the metabolic syndrome, consisting of inflammation, hypertension, dyslipidemia and insulin resistance. In turn, these metabolic abnormalities cause cerebrovascular dysfunction, which may cause white and grey matter tissue loss and consequent cognitive impairment. While there have been several neuroimaging studies linking adiposity to changes in brain morphometry, a comprehensive investigation of the relationship has so far not been done. Here we use structural equation modelling applied to over 15,000 individuals from the UK Biobank to identify the causal chain that links adiposity to cognitive dysfunction. We found that body mass index and waist-to-hip ratio were positively related to higher plasma C-reactive protein, dyslipidemia, occurrence of hypertension and diabetes, all of which were in turn related to cerebrovascular disease as measured by volume of white matter hyperintensities on magnetic resonance imaging. White mater hyperintensities were associated with lower cortical thickness and volume and higher subcortical volumes, which were associated with cognitive deficits on tests of visuospatial memory, fluid intelligence, and working memory among others. In follow-up analyses we found that inflammation, hypertension and diabetes mediated 20% of the relationship between obesity and cerebrovascular disease and that cerebrovascular disease mediated a significant proportion of the relationship between obesity and cortical thickness and volume. We also showed that volume of white matter hyperintensities was related to decreased fractional anisotropy and increased mean diffusivity in the majority of white matter tracts, pointing to white matter dysconnectivity as a major cause of impaired cognition. Our results have clinical implications, supporting a role for the management of adiposity in the prevention of late-life dementia and cognitive decline.

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Probing the aggregated effects of purifying selection per individual on 1,380 medical phenotypes in the UK Biobank

PLoS Genetics ◽

10.1371/journal.pgen.1009337 ◽

2021 ◽

Vol 17 (1) ◽

pp. e1009337

Author(s):

Ha My T. Vy ◽

Daniel M. Jordan ◽

Daniel J. Balick ◽

Ron Do

Keyword(s):

Natural Selection ◽

Strong Association ◽

Purifying Selection ◽

Relative Fitness ◽

Uk Biobank ◽

Multiple Test Correction ◽

Multiple Test ◽

The Uk ◽

The Relationship ◽

Statistical Metrics

Understanding the relationship between natural selection and phenotypic variation has been a long-standing challenge in human population genetics. With the emergence of biobank-scale datasets, along with new statistical metrics to approximate strength of purifying selection at the variant level, it is now possible to correlate a proxy of individual relative fitness with a range of medical phenotypes. We calculated a per-individual deleterious load score by summing the total number of derived alleles per individual after incorporating a weight that approximates strength of purifying selection. We assessed four methods for the weight, including GERP, phyloP, CADD, and fitcons. By quantitatively tracking each of these scores with the site frequency spectrum, we identified phyloP as the most appropriate weight. The phyloP-weighted load score was then calculated across 15,129,142 variants in 335,161 individuals from the UK Biobank and tested for association on 1,380 medical phenotypes. After accounting for multiple test correction, we observed a strong association of the load score amongst coding sites only on 27 traits including body mass, adiposity and metabolic rate. We further observed that the association signals were driven by common variants (derived allele frequency > 5%) with high phyloP score (phyloP > 2). Finally, through permutation analyses, we showed that the load score amongst coding sites had an excess of nominally significant associations on many medical phenotypes. These results suggest a broad impact of deleterious load on medical phenotypes and highlight the deleterious load score as a tool to disentangle the complex relationship between natural selection and medical phenotypes.

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