The Relationship Between Glycaemia, Cognitive Function, Structural Brain Outcomes and Dementia: A Mendelian Randomisation Study in the UK Biobank

Diabetes ◽  
2021 ◽  
pp. db200895
Author(s):  
Victoria Garfield ◽  
Aliki-Eleni Farmaki ◽  
Ghazaleh Fatemifar ◽  
Sophie V. Eastwood ◽  
Rohini Mathur ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Mendelian Randomisation ◽  
Uk Biobank ◽  
The Uk ◽  
The Relationship ◽  
Structural Brain

A life course approach to elucidate the role of adiposity in asthma risk: evidence from a Mendelian randomisation study

2020 ◽  
pp. jech-2020-213745
Author(s):  
Shiu Lun Au Yeung ◽  
Albert Martin Li ◽  
C Mary Schooling
Keyword(s):  
Childhood Obesity ◽  
Life Course ◽  
Life Course Perspective ◽  
Mendelian Randomisation ◽  
Uk Biobank ◽  
Asthma Risk ◽  
A Genome ◽  
The Uk ◽  
The Relationship

BackgroundAdiposity is associated with asthma although studies do not usually explore the inter-related role of childhood and adult adiposity in asthma risk using a life course perspective.MethodsWe conducted a Mendelian randomisation (MR) study using genetic instruments for childhood body mass index (BMI) (n=47 541), childhood obesity (n=29 822) and adult BMI (n=681 725) applied to the UK Biobank (n=401 837), with validation in a genome-wide association study of asthma (GABRIEL, n=5616). We used inverse variance weighting and other sensitivity analyses to examine the relationship between adiposity and asthma risk. We assessed mediation using multivariable Mendelian randomisation (MVMR) analysis.ResultsChildhood BMI was related to asthma in the UK Biobank (OR 1.10 per SD increase, 95% CI 0.99 to 1.22). Adult BMI was associated with asthma risk (OR 1.33 per SD increase, 95% CI 1.25 to 1.43). Analyses in GABRIEL gave directionally consistent results but with wide CI. The relationship between childhood obesity and asthma risk was less clear in both data sources. MVMR suggested the relation of childhood BMI with asthma risk was largely mediated via adult BMI.ConclusionAdiposity in childhood likely cause asthma, but the effect is primarily mediated via adult BMI.

scholarly journals Is there an association between daytime napping and cognitive function? A Mendelian randomisation study in the UK Biobank

2021 ◽  
Author(s):  
Valentina Paz ◽  
Hassan S Dashti ◽  
Victoria Garfield
Keyword(s):  
Reaction Time ◽  
Cognitive Function ◽  
Visual Memory ◽  
Sleep Apnoea ◽  
Cognitive Outcomes ◽  
Sensitivity Analyses ◽  
Mendelian Randomisation ◽  
Uk Biobank ◽  
Weighted Median ◽  
The Uk

Background: Daytime napping has been associated with cognitive function in observational studies. However, it remains elusive whether napping could be beneficial or detrimental for cognition and whether these associations are causal. Methods: Using Mendelian randomisation (MR), we studied the relationship between daytime napping and cognitive outcomes. Data were from UK Biobank (n= 378,932; mean age= 57 years). Our exposure (daytime napping) was instrumented using 92 genome-wide, independent genetic variants and our cognitive outcomes were reaction time and visual memory. Inverse-variance weighted MR was implemented, with sensitivity analyses including MR-Egger and the Weighted Median Estimator for horizontal pleiotropy. We also tested different daytime napping instruments (47 SNPs, 86 SNPs and 17 SNPs) to ensure the robustness of our results. Results: No associations were found between daytime napping and reaction time (expβ=1.01, 95%CI=1.00; 1.03), or visual memory (expβ=0.99, 95%CI=0.94; 1.05). MR-Egger and Weighted Median Estimator approaches showed no evidence of horizontal pleiotropy. Additional analyses with 47 SNPs (adjusted for excessive daytime sleepiness), 86 SNPs (excluding sleep apnoea) and 17 SNPs (no sample overlap with UKB) also showed no associations with reaction time or visual memory. Conclusions: Overall, we observed no evidence of a causal association between habitual daytime napping and reaction time and visual memory. Future studies should focus on the associations between napping and other cognitive outcomes.

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

2019 ◽  
Vol 176 (7) ◽  
pp. 573-574 ◽  
Author(s):  
Rebecca B. Lawn ◽  
Hannah M. Sallis ◽  
Amy E. Taylor ◽  
Robyn E. Wootton ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Common Variant ◽  
Uk Biobank ◽  
The Uk ◽  
The Relationship

scholarly journals Caffeinated Coffee and Tea Consumption, Genetic Variation and Cognitive Function in the UK Biobank

2020 ◽  
Vol 150 (8) ◽  
pp. 2164-2174
Author(s):  
Marilyn C Cornelis ◽  
Sandra Weintraub ◽  
Martha Clare Morris
Keyword(s):  
Genetic Variation ◽  
Cognitive Function ◽  
Poor Performance ◽  
Sociodemographic Factors ◽  
Caffeine Intake ◽  
Tea Consumption ◽  
Uk Biobank ◽  
Trail Making ◽  
Caffeine Metabolism ◽  
The Uk

ABSTRACT Background Coffee and tea are the major contributors of caffeine in the diet. Evidence points to the premise that caffeine may benefit cognition. Objective We examined the associations of habitual regular coffee or tea and caffeine intake with cognitive function whilst additionally accounting for genetic variation in caffeine metabolism. Methods We included white participants aged 37–73 y from the UK Biobank who provided biological samples and completed touchscreen questionnaires regarding sociodemographic factors, medical history, lifestyle, and diet. Habitual caffeine-containing coffee and tea intake was self-reported in cups/day and used to estimate caffeine intake. Between 97,369 and 445,786 participants with data also completed ≥1 of 7 self-administered cognitive functioning tests using a touchscreen system (2006–2010) or on home computers (2014). Multivariable regressions were used to examine the association between coffee, tea, or caffeine intake and cognition test scores. We also tested interactions between coffee, tea, or caffeine intake and a genetic-based caffeine-metabolism score (CMS) on cognitive function. Results After multivariable adjustment, reaction time, Pairs Matching, Trail Making test B, and symbol digit substitution, performance significantly decreased with consumption of 1 or more cups of coffee (all tests P-trend < 0.0001). Tea consumption was associated with poor performance on all tests (P-trend < 0.0001). No statistically significant CMS × tea, CMS × coffee, or CMS × caffeine interactions were observed. Conclusions Our findings, based on the participants of the UK Biobank, provide little support for habitual consumption of regular coffee or tea and caffeine in improving cognitive function. On the contrary, we observed decrements in performance with intakes of these beverages which may be a result of confounding. Whether habitual caffeine intake affects cognitive function therefore remains to be tested.

scholarly journals Genetic predisposition to increased serum calcium, bone mineral density, and fracture risk in individuals with normal calcium levels: mendelian randomisation study

BMJ ◽  
2019 ◽  
pp. l4410 ◽  
Author(s):  
Agustin Cerani ◽  
Sirui Zhou ◽  
Vincenzo Forgetta ◽  
John A Morris ◽  
Katerina Trajanoska ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Serum Calcium ◽  
Genetic Predisposition ◽  
Calcium Supplementation ◽  
Meta Analysis ◽  
Mendelian Randomisation ◽  
Uk Biobank ◽  
Mineral Density ◽  
The Uk

Abstract Objective To determine if genetically increased serum calcium levels are associated with improved bone mineral density and a reduction in osteoporotic fractures. Design Mendelian randomisation study. Setting Cohorts used included: the UK Biobank cohort, providing genotypic and estimated bone mineral density data; 25 cohorts from UK, USA, Europe, and China, providing genotypic and fracture data; and 17 cohorts from Europe, providing genotypic and serum calcium data (summary level statistics). Participants A genome-wide association meta-analysis of serum calcium levels in up to 61 079 individuals was used to identify genetic determinants of serum calcium levels. The UK Biobank study was used to assess the association of genetic predisposition to increased serum calcium with estimated bone mineral density derived from heel ultrasound in 426 824 individuals who had, on average, calcium levels in the normal range. A fracture genome-wide association meta-analysis comprising 24 cohorts and the UK Biobank including a total of 76 549 cases and 470 164 controls, who, on average, also had calcium levels in the normal range was then performed. Results A standard deviation increase in genetically derived serum calcium (0.13 mmol/L or 0.51 mg/dL) was not associated with increased estimated bone mineral density (0.003 g/cm 2 , 95% confidence interval −0.059 to 0.066; P=0.92) or a reduced risk of fractures (odds ratio 1.01, 95% confidence interval 0.89 to 1.15; P=0.85) in inverse-variance weighted mendelian randomisation analyses. Sensitivity analyses did not provide evidence of pleiotropic effects. Conclusions Genetic predisposition to increased serum calcium levels in individuals with normal calcium levels is not associated with an increase in estimated bone mineral density and does not provide clinically relevant protection against fracture. Whether such predisposition mimics the effect of short term calcium supplementation is not known. Given that the same genetically derived increase in serum calcium is associated with an increased risk of coronary artery disease, widespread calcium supplementation in the general population could provide more risk than benefit.

scholarly journals Polynomial Mendelian Randomization reveals widespread non-linear causal effects in the UK Biobank

2021 ◽  
Author(s):  
Jonathan Sulc ◽  
Jenny Sjaarda ◽  
Zoltan Kutalik
Keyword(s):  
Causal Inference ◽  
Large Scale ◽  
Causal Effect ◽  
Causal Effects ◽  
Mendelian Randomisation ◽  
Uk Biobank ◽  
Individual Level ◽  
Glucose Levels ◽  
Causal Function ◽  
The Uk

Causal inference is a critical step in improving our understanding of biological processes and Mendelian randomisation (MR) has emerged as one of the foremost methods to efficiently interrogate diverse hypotheses using large-scale, observational data from biobanks. Although many extensions have been developed to address the three core assumptions of MR-based causal inference (relevance, exclusion restriction, and exchangeability), most approaches implicitly assume that any putative causal effect is linear. Here we propose PolyMR, an MR-based method which provides a polynomial approximation of an (arbitrary) causal function between an exposure and an outcome. We show that this method provides accurate inference of the shape and magnitude of causal functions with greater accuracy than existing methods. We applied this method to data from the UK Biobank, testing for effects between anthropometric traits and continuous health-related phenotypes and found most of these (84%) to have causal effects which deviate significantly from linear. These deviations ranged from slight attenuation at the extremes of the exposure distribution, to large changes in the magnitude of the effect across the range of the exposure (e.g. a 1 kg/m2 change in BMI having stronger effects on glucose levels if the initial BMI was higher), to non-monotonic causal relationships (e.g. the effects of BMI on cholesterol forming an inverted U shape). Finally, we show that the linearity assumption of the causal effect may lead to the misinterpretation of health risks at the individual level or heterogeneous effect estimates when using cohorts with differing average exposure levels.

scholarly journals Consumption of Red Meat Is Negatively Associated with Cognitive Function: A Cross-Sectional Analysis of UK Biobank

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1510-1510
Author(s):  
Huifeng Zhang ◽  
Janet Cade ◽  
Laura Hadie
Keyword(s):  
Cognitive Function ◽  
Prospective Memory ◽  
Red Meat ◽  
Uk Biobank ◽  
Cross Sectional ◽  
Meat Intake ◽  
Visual Spatial ◽  
Additional Portion ◽  
The Uk ◽  
Sectional Analysis

Abstract Objectives In the largest study of its type, we tested for associations between red meat consumption and cognitive function using data from half a million participants enrolled into the UK Biobank cohort study. Methods Baseline data was obtained from the UK Biobank cohort, comprising half a million participants aged 37–73 years recruited between 2006 and 2010. The intake of red meat (frequency per week) was obtained using a self-reported food frequency questionnaire. Cognitive tests included the reaction-time (RT) test (reaction ability, N = 496, 695), fluid intelligence (FI) (reasoning ability, N = 165,467), the numeric memory test (short-term memory, N = 50,364), the pairs-matching (PM) test (visual-spatial memory, N = 482,650) and the prospective memory test (N = 171,509). Logistic and linear regression modelling was conducted with adjustment for potential confounders including age at recruitment, sex, ethnicity, Townsend deprivation index, smoking, alcohol, education, body mass index, physical activity level, sleeping hours, stroke history, and family history of dementia. Results Each additional portion per week of red-meat intake was associated with slower reaction time by 0.26 milliseconds (95% CI: 0.02, 0.50), lower FI score by 0.01 points (−0.02, −0.00), reduced numeric memory by 0.02 digits (−0.03, −0.01), and increased odds of incorrect prospective memory by 1% (0%, 2%). In men these associations were larger regarding the RT test (β = 0.54, [0.21, 0.87]), FI score (β = −0.02, [−0.03, −0.01]), and prospective memory (OR = 1.03, [1.01, 1.04]), while in women these were not significant. In terms of the PM test, a single additional portion of red-meat intake was associated with reduced incorrect matches by 0.004 pairs (−0.003, −0.006), both in men (β = −0.003, [−0.001, −0.005]) and women (β = −0.006, [−0.004, −0.008]). Conclusions In this cross-sectional analysis of the adult UK population, higher intake of red meat was associated with poorer cognitive function including reaction and reasoning ability, short-term and prospective memory especially among men; but not visual-spatial memory which showed a weak protective effect of red meat. Funding Sources The joint scholarship of University of Leeds and China Scholarship Council.

Sign in / Sign up

Export Citation Format

Share Document