scholarly journals Testing for Interactions Between APOE and Klotho Genotypes on Cognitive, Dementia, and Brain Imaging Metrics in UK Biobank

2021 ◽  
pp. 1-5
Author(s):  
Rachana Tank ◽  
Joey Ward ◽  
Carlos Celis-Morales ◽  
Daniel J. Smith ◽  
Kristin E. Flegal ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Cognitive Impairment ◽  
Brain Imaging ◽  
Brain Structure ◽  
Cognitive Abilities ◽  
Uk Biobank ◽  
Increased Risk ◽  
Versus Risk

Recent research suggests genetic variation in the Klotho locus may modify the association between APOE ɛ4 and cognitive impairment. We tested for associations and interactions between these genotypes versus risk of dementia, cognitive abilities, and brain structure in older UK Biobank participants. Klotho status was indexed with rs9536314 heterozygosity (versus not), in unrelated people with versus without APOE ɛ4 genotype, corrected for various confounders. APOE ɛ4 associated with increased risk of dementia, worse cognitive abilities, and brain structure. Klotho was associated with better reasoning. There were no interactions; potentially suggesting an age- and pathology-dependent Klotho effect.

scholarly journals Lack of evidence for interactions between APOE and Klotho genotypes on cognitive, dementia and brain imaging metrics in UK Biobank

2021 ◽  
Author(s):  
Rachana Tank ◽  
Joey Ward ◽  
Daniel J. Smith ◽  
Kristin E. Flegal ◽  
Donald M. Lyall
Keyword(s):  
Cognitive Impairment ◽  
Brain Imaging ◽  
Brain Structure ◽  
Cognitive Abilities ◽  
Large Scale ◽  
Cognitive Test ◽  
Uk Biobank ◽  
Type 1 Error ◽  
Structural Brain

AbstractImportanceRecent research has suggested that genetic variation in the Klotho (KL) locus may modify the association between apolipoprotein e (APOE) e4 genotype and cognitive impairment.ObjectiveLarge-scale testing for associations and interactions between KL and APOE genotypes vs. risk of dementia (n=1,570 cases), cognitive abilities (n=174,513) and brain structure (n = 13,158) in older (60+ years) participants.Design, setting and participantsCross-sectional and prospective data (UK Biobank).Main outcomes and measuresKL status was indexed with heterozygosity of the rs9536314 polymorphism (vs. not), in unrelated people with vs. without APOE e4 genotype, using regression and interaction tests. We assessed non-demented cognitive scores (processing speed; reasoning; memory; executive function), multiple structural brain imaging, and clinical dementia outcomes. All tests were corrected for age, sex, assessment centre, eight principal components for population stratification, genotypic array, smoking history, deprivation, and self-reported medication history.ResultsAPOE e4 presence (vs. not) was associated with increased risk of dementia, worse cognitive abilities and brain structure differences. KL heterozygosity was associated with less frontal lobe grey matter. There were no significant APOE/KL interactions for cognitive, dementia or brain imaging measures (all P>0.05).Conclusions and relevanceWe found no evidence of APOE/KL interactions on cognitive, dementia or brain imaging outcomes. This could be due to some degree of cognitive test imprecision, generally preserved participant health potentially due to relatively young age, type-1 error in prior studies, or indicative of a significant age-dependent KL effect only in the context of marked AD pathology.Key pointsQuestion: Klotho genotype has been previously shown to ‘offset’ a substantial amount of the APOE e4/cognitive impairment association. Is this modification effect apparent in large-scale independent data, in terms of non-demented cognitive abilities, brain structure and dementia prevalence?Findings: In aged 60 years and above participants from UK Biobank, we found significant associations of APOE and Klotho genotypes on cognitive, structural brain and dementia outcomes, but no significant interactions.Meaning: This could reflect somewhat healthy participants, prior type 1 error or cognitive/dementia ascertainment imprecision, and/or that Klotho genotypic effects are age and neuropathology dependent.

scholarly journals Associations of cigarette smoking with gray and white matter in the UK Biobank

2019 ◽  
Author(s):  
Joshua Gray ◽  
Matthew Thompson ◽  
Chelsie Benca-Bachman ◽  
Max Michael Owens ◽  
Mikela Murphy ◽  
...  
Keyword(s):  
White Matter ◽  
Cigarette Smoking ◽  
Gray Matter ◽  
Brain Structure ◽  
Mean Diffusivity ◽  
Medial Lemniscus ◽  
Uk Biobank ◽  
Matter Volume ◽  
Increased Risk ◽  
The Uk

Chronic cigarette smoking is associated with increased risk for myriad health consequences including cognitive decline and dementia, but research on the link between smoking and brain structure is nascent. We assessed the relationship of cigarette smoking (ever smoked, cigarettes per day, and duration) with gray and white matter using the UK Biobank cohort (gray matter N = 19,615; white matter N = 17,760), adjusting for numerous demographic and health confounders. Ever smoked and duration were associated with smaller total gray matter volume. Ever smoked was associated with reduced volume of the right VIIIa cerebellum, as well as elevated white matter hyperintensity volumes. Smoking duration was associated with reduced total white matter volume. With regard to specific tracts, ever smoked was associated with reduced fractional anisotropy in the left cingulate gyrus part of the cingulum, left posterior thalamic radiation, and bilateral superior thalamic radiation and increased mean diffusivity in the middle cerebellar peduncle, right medial lemniscus, bilateral posterior thalamic radiation, and bilateral superior thalamic radiation. Overall, we found significant associations of cigarette exposure with global measures of gray and white matter. Furthermore, we found select associations of ever smoked, but not cigarettes per day or duration, with specific gray and white matter regions. These findings inform our understanding of the connections between smoking and variation in brain structure and clarify potential mechanisms of risk for common neurological sequelae.

scholarly journals Altered Cortical Brain Structure and Increased Risk for Disease Seen Decades After Perinatal Exposure to Maternal Smoking: A Study of 9000 Adults in the UK Biobank

2019 ◽  
Vol 29 (12) ◽  
pp. 5217-5233 ◽  
Author(s):  
Lauren E Salminen ◽  
Rand R Wilcox ◽  
Alyssa H Zhu ◽  
Brandalyn C Riedel ◽  
Christopher R K Ching ◽  
...  
Keyword(s):  
Brain Structure ◽  
Brain Mri ◽  
Population Based ◽  
Smoke Exposure ◽  
Sensitivity Analyses ◽  
Uk Biobank ◽  
Increased Risk ◽  
Increase Risk ◽  
Sensory Cortices ◽  
The Uk

Abstract Secondhand smoke exposure is a major public health risk that is especially harmful to the developing brain, but it is unclear if early exposure affects brain structure during middle age and older adulthood. Here we analyzed brain MRI data from the UK Biobank in a population-based sample of individuals (ages 44–80) who were exposed (n = 2510) or unexposed (n = 6079) to smoking around birth. We used robust statistical models, including quantile regressions, to test the effect of perinatal smoke exposure (PSE) on cortical surface area (SA), thickness, and subcortical volumes. We hypothesized that PSE would be associated with cortical disruption in primary sensory areas compared to unexposed (PSE−) adults. After adjusting for multiple comparisons, SA was significantly lower in the pericalcarine (PCAL), inferior parietal (IPL), and regions of the temporal and frontal cortex of PSE+ adults; these abnormalities were associated with increased risk for several diseases, including circulatory and endocrine conditions. Sensitivity analyses conducted in a hold-out group of healthy participants (exposed, n = 109, unexposed, n = 315) replicated the effect of PSE on SA in the PCAL and IPL. Collectively our results show a negative, long term effect of PSE on sensory cortices that may increase risk for disease later in life.

scholarly journals Genome-wide association studies of brain structure and function in the UK Biobank

2017 ◽  
Author(s):  
Lloyd T. Elliott ◽  
Kevin Sharp ◽  
Fidel Alfaro-Almagro ◽  
Sinan Shi ◽  
Karla Miller ◽  
...  
Keyword(s):  
Brain Imaging ◽  
Brain Structure ◽  
Association Studies ◽  
Structure And Function ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Genome Wide ◽  
Brain Structure And Function ◽  
And Function

SummaryThe genetic basis of brain structure and function is largely unknown. We carried out genome-wide association studies of 3,144 distinct functional and structural brain imaging derived phenotypes in UK Biobank (discovery dataset 8,428 subjects). We show that many of these phenotypes are heritable. We identify 148 clusters of SNP-imaging associations with lead SNPs that replicate at p<0.05, when we would expect 21 to replicate by chance. Notable significant and interpretable associations include: iron transport and storage genes, related to changes in T2* in subcortical regions; extracellular matrix and the epidermal growth factor genes, associated with white matter micro-structure and lesion volume; genes regulating mid-line axon guidance development associated with pontine crossing tract organisation; and overall 17 genes involved in development, pathway signalling and plasticity. Our results provide new insight into the genetic architecture of the brain with relevance to complex neurological and psychiatric disorders, as well as brain development and aging. The full set of results is available on the interactive Oxford Brain Imaging Genetics (BIG) web browser.

scholarly journals Exploring the Role of Contactins across Psychological, Psychiatric and Cardiometabolic Traits within UK Biobank

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1326
Author(s):  
Julia Morris ◽  
Soddy Sau Yu Leung ◽  
Mark E.S. Bailey ◽  
Breda Cullen ◽  
Amy Ferguson ◽  
...  
Keyword(s):  
Mental Illness ◽  
Genetic Variation ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Psychological Traits ◽  
Medication Effects ◽  
Increased Risk ◽  
Wide Range ◽  
Shared Risk

Individuals with severe mental illness have an increased risk of cardiometabolic diseases compared to the general population. Shared risk factors and medication effects explain part of this excess risk; however, there is growing evidence to suggest that shared biology (including genetic variation) is likely to contribute to comorbidity between mental and physical illness. Contactins are a family of genes involved in development of the nervous system and implicated, though genome-wide association studies, in a wide range of psychological, psychiatric and cardiometabolic conditions. Contactins are plausible candidates for shared pathology between mental and physical health. We used data from UK Biobank to systematically assess how genetic variation in contactin genes was associated with a wide range of psychological, psychiatric and cardiometabolic conditions. We also investigated whether associations for cardiometabolic and psychological traits represented the same or distinct signals and how the genetic variation might influence the measured traits. We identified: A novel genetic association between variation in CNTN1 and current smoking; two independent signals in CNTN4 for BMI; and demonstrated that associations between CNTN5 and neuroticism were distinct from those between CNTN5 and blood pressure/HbA1c. There was no evidence that the contactin genes contributed to shared aetiology between physical and mental illness

scholarly journals Long-Term Outcomes in Stroke Patients with Cognitive Impairment: A Population-Based Study

Geriatrics ◽  
2020 ◽  
Vol 5 (2) ◽  
pp. 32 ◽  
Author(s):  
Majed Obaid ◽  
Clare Flach ◽  
Iain Marshall ◽  
Charles D. A. Wolfe ◽  
Abdel Douiri
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Cognitive Abilities ◽  
Population Based ◽  
Post Stroke ◽  
Relative Risks ◽  
Stroke Population ◽  
Increased Risk ◽  
One Year ◽  
State Examination

This study assesses five year outcomes of patients with cognitive deficits within the first three months after stroke. Population-based data from the South London Stroke Register between 1995 and 2018 were studied. Cognitive function was assessed using the Abbreviated-Mental-Test or Mini-Mental-State-Examination. Multivariable Poisson regression models with robust standard errors were constructed, to evaluate relative risks (RRs) and associations between post-stroke deterioration in cognitive function during the first three months on dependency, mortality, depression and institutionalisation. A total of 6504 patients with first-ever strokes were registered with a mean age of 73 (SD: 13.2). During the first three months post-stoke, approximately one-third of these stroke survivors either cognitively improved (37%), deteriorated (30%) or remained unchanged (33%). Post-stroke cognitive impairment was associated with increases, in five years, of the risks of mortality, dependency, depression and being institutionalised by RRs 30% (95% confidence interval: 1.1–1.5), 90% (1.3–2.6), 60% (1.1–2.4) and 50% (1.1–2.3), respectively. Deterioration in cognitive function by 10% or more between seven days and three months was associated with an approximate two-fold increased risk in mortality, dependency, and being institutionalised after one year, compared to stable cognitive function; RRs 80% (1.1–3.0), 70% (1.2–2.4) and two-fold (1.3–3.2), respectively. Monitoring further change to maintain cognitive abilities should be a focus to improve outcomes.

scholarly journals Altered cortical brain structure and increased risk for disease seen decades after perinatal exposure to maternal smoking: A study of 9,000 adults in the UK Biobank

2018 ◽  
Author(s):  
Lauren E. Salminen ◽  
Rand R. Wilcox ◽  
Alyssa H. Zhu ◽  
Brandalyn C. Riedel ◽  
Christopher R. K. Ching ◽  
...  
Keyword(s):  
Brain Structure ◽  
Brain Mri ◽  
Population Based ◽  
Smoke Exposure ◽  
Sensitivity Analyses ◽  
Uk Biobank ◽  
Increased Risk ◽  
Increase Risk ◽  
Sensory Cortices ◽  
The Uk

AbstractSecondhand smoke exposure is a major public health risk that is especially harmful to the developing brain, but it is unclear if early exposure affects brain structure during middle age and older adulthood. Here we analyzed brain MRI data from the UK Biobank in a population-based sample of individuals (ages 44-80) who were exposed (n=2,510) or unexposed (n=6,079) to smoking around birth. We used robust statistical models, including quantile regressions, to test the effect of perinatal smoke exposure (PSE) on cortical surface area (SA), thickness, and subcortical volume. We hypothesized that PSE would be associated with cortical disruption in primary sensory areas compared to unexposed (PSE-) adults. After adjusting for multiple comparisons, SA was significantly lower in the pericalcarine (PCAL), inferior parietal (IPL), and regions of the temporal and frontal cortex of PSE+adults; these abnormalities were associated with increased risk for several diseases, including circulatory and endocrine conditions. Sensitivity analyses conducted in a hold-out group of healthy participants (exposed, n=109, unexposed, n=315) replicated the effect of PSE on SA in the PCAL and IPL. Collectively our results show a negative, long term effect of PSE on sensory cortices that may increase risk for disease later in life.

Genetic variation in NFE2L2 and SEPS1S associated with increased risk of Hashimoto's thyroiditis

2017 ◽  
Author(s):  
Liliana R Santos ◽  
Cecila Duraes ◽  
Ana Pestana ◽  
Cesar Esteves ◽  
Celestino Neves ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Hashimoto’S Thyroiditis ◽  
Hashimoto's Thyroiditis ◽  
Increased Risk

Association of Circulating Cholesterol Level with Cognitive Function and Mild Cognitive Impairment in the Elderly: A Community-based Population Study

2020 ◽  
Vol 17 (6) ◽  
pp. 556-565
Author(s):  
Yujie Guo ◽  
Pengfei Li ◽  
Xiaojun Ma ◽  
Xiaochen Huang ◽  
Zhuoheng Liu ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Function ◽  
Cholesterol Level ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Cross Sectional ◽  
Increased Risk ◽  
Aging Adults ◽  
Female Subjects

Background: The present study was designed to examine the association of circulating cholesterol with cognitive function in non-demented community aging adults. Methods: This was a cross-sectional study including 1754 Chinese adults aged 55-80 years. The association between serum cholesterol levels and cognitive function was examined. Participants were categorized into four groups according to the quartile of circulating TC (total cholesterol), High Density Lipoprotein Cholesterol (HDL-c), Low Density Lipoprotein Cholesterol (LDL-c) levels and HDLc/ LDL-c ratio. The difference in cognitive performance among the groups was compared. Logistic regression model was used to determine the association of circulating cholesterol level with the risk of Mild Cognitive Impairment (MCI). Results: Mild increase of serum LDL-c level correlated with better visual and executive, language, memory and delayed recall abilities. Higher circulating TC and HDL-c levels were found to be associated with poorer cognitive function, especially in aging female subjects. Higher circulating TC, HDL-c and HDL/LDL ratio indicated an increased risk of MCI, especially in female subjects. Conclusion: Slight increase in circulating LDL-c level might benefit cognitive function in aging adults. However, higher circulating TC and HDL-c levels might indicate a decline of cognitive function, especially in aging female subjects.

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