scholarly journals Les pièges de l’amélioration

2019 ◽  
Vol 35 (8-9) ◽  
pp. 709-711 ◽  
Author(s):  
Bertrand Jordan
Keyword(s):  
Survival Analysis ◽  
Hiv Infection ◽  
Population Data ◽  
Positive Change ◽  
Genetic Enhancement ◽  
Human Embryos ◽  
Uk Biobank ◽  
Negative Effects ◽  
Germline Modification ◽  
The Uk

Inactivation of the CCR5 gene by CRISPR editing in human embryos, as recently attempted in China, was touted as a positive change for the babies involved since it was expected to impart resistance to HIV infection. However, it turns out that the absence of CCR5 is not neutral but actually decreases fitness, as shown by survival analysis of population data in the UK biobank. This underlines the pitfalls of genetic enhancement, and emphasizes that any germline modification must be preceded by in-depth studies to exclude unforeseen negative effects. ‡

scholarly journals Automated localization and quality control of the aorta in cine CMR can significantly accelerate processing of the UK Biobank population data

PLoS ONE ◽  
2019 ◽  
Vol 14 (2) ◽  
pp. e0212272 ◽  
Author(s):  
Luca Biasiolli ◽  
Evan Hann ◽  
Elena Lukaschuk ◽  
Valentina Carapella ◽  
Jose M. Paiva ◽  
...  
Keyword(s):  
Quality Control ◽  
Population Data ◽  
Uk Biobank ◽  
The Uk ◽  
Cine Cmr

scholarly journals Identification of 13 independent genetic loci associated with cognitive resilience in healthy aging in 330,097 individuals in the UK Biobank

2021 ◽  
Author(s):  
Joan Fitzgerald ◽  
Laura Fahey ◽  
Laurena Holleran ◽  
Pilib Ó Broin ◽  
Gary Donohoe ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Genome Wide Association Study ◽  
Cell Types ◽  
Brain Regions ◽  
Specific Cell ◽  
Uk Biobank ◽  
Negative Effects ◽  
Genome Wide ◽  
A Genome ◽  
The Uk

AbstractCognitive resilience is the ability to withstand the negative effects of stress on cognitive functioning and is important for maintaining quality of life while aging. Here we employed a proxy phenotype approach to create a longitudinal cognitive resilience phenotype using past education years and current processing speed, reflecting an average time span of 40 years, in 330,097 individuals from the UK Biobank. A genome-wide association study identified 13 independent genome-wide significant loci that implicate 33 genes. A portion of resilience’s genetic signal is distinct from the genetics of intelligence. Functional analyses showed enrichment in several brain regions and involvement of specific cell types, including GABAergic neurons (P=6.59×10−8) and glutamatergic neurons (P=6.98×10−6) in the cortex. Gene-set analyses implicated the biological process “neuron differentiation” (P=9.7×10−7) and the cellular component “synaptic part” (P=2.14×10−6). Mendelian randomization analysis showed a causative effect of white matter volume on cognitive resilience. These results enhance neurobiological understanding of resilience.

scholarly journals Blood pressure and bladder cancer risk in men by use of survival analysis and in interaction with NAT2 genotype, and by Mendelian randomization analysis

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241711
Author(s):  
Stanley Teleka ◽  
George Hindy ◽  
Isabel Drake ◽  
Alaitz Poveda ◽  
Olle Melander ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Bladder Cancer ◽  
Survival Analysis ◽  
Mendelian Randomization ◽  
Cox Regression ◽  
Least Square ◽  
Weighted Estimate ◽  
Uk Biobank ◽  
Muscle Invasive ◽  
The Uk

The association between blood pressure (BP) and bladder cancer (BC) risk remains unclear with confounding by smoking being of particular concern. We investigated the association between BP and BC risk among men using conventional survival-analysis, and by Mendelian Randomization (MR) analysis in an attempt to disconnect the association from smoking. We additionally investigated the interaction between BP and N-acetyltransferase-2 (NAT2) rs1495741, an established BC genetic risk variant, in the association. Populations consisting of 188,167 men with 502 incident BC’s in the UK-biobank and 27,107 men with 928 incident BC’s in two Swedish cohorts were used for the analysis. We found a positive association between systolic BP and BC risk in Cox-regression survival analysis in the Swedish cohorts, (hazard ratio [HR] per standard deviation [SD]: 1.14 [95% confidence interval 1.05–1.22]) and MR analysis (odds ratio per SD: 2-stage least-square regression, 7.70 [1.92–30.9]; inverse-variance weighted estimate, 3.43 [1.12–10.5]), and no associations in the UK-biobank (HR systolic BP: 0.93 [0.85–1.02]; MR OR: 1.24 [0.35–4.40] and 1.37 [0.43–4.37], respectively). BP levels were positively associated with muscle-invasive BC (MIBC) (HRs: systolic BP, 1.32 [1.09–1.59]; diastolic BP, 1.27 [1.04–1.55]), but not with non-muscle invasive BC, which could be analyzed in the Swedish cohorts only. There was no interaction between BP and NAT2 in relation to BC on the additive or multiplicative scale. These results suggest that BP might be related to BC, more particularly MIBC. There was no evidence to support interaction between BP and NAT2 in relation to BC in our study.

Low birthweight is associated with poorer limb muscle mass and grip strength in middle age: findings from the UK Biobank Imaging Enhancement

2019 ◽  
Author(s):  
Elizabeth Curtis ◽  
Justin Liu ◽  
Kate Ward ◽  
Karen Jameson ◽  
Zahra Raisi-Estabragh ◽  
...  
Keyword(s):  
Grip Strength ◽  
Muscle Mass ◽  
Low Birthweight ◽  
Middle Age ◽  
Limb Muscle ◽  
Uk Biobank ◽  
The Uk

Contrasting Broad- and Clinically- defined Polygenic Indicators of Depression and Depression-related Phenotypes in Adults and Children

2020 ◽  
Author(s):  
John E. McGeary ◽  
Chelsie Benca-Bachman ◽  
Victoria Risner ◽  
Christopher G Beevers ◽  
Brandon Gibb ◽  
...  
Keyword(s):  
Suicidal Ideation ◽  
Cognitive Reappraisal ◽  
Twin Studies ◽  
European Ancestry ◽  
Summary Statistics ◽  
Depression Severity ◽  
Uk Biobank ◽  
Polygenic Scores ◽  
Adults And Children ◽  
The Uk

Twin studies indicate that 30-40% of the disease liability for depression can be attributed to genetic differences. Here, we assess the explanatory ability of polygenic scores (PGS) based on broad- (PGSBD) and clinical- (PGSMDD) depression summary statistics from the UK Biobank using independent cohorts of adults (N=210; 100% European Ancestry) and children (N=728; 70% European Ancestry) who have been extensively phenotyped for depression and related neurocognitive phenotypes. PGS associations with depression severity and diagnosis were generally modest, and larger in adults than children. Polygenic prediction of depression-related phenotypes was mixed and varied by PGS. Higher PGSBD, in adults, was associated with a higher likelihood of having suicidal ideation, increased brooding and anhedonia, and lower levels of cognitive reappraisal; PGSMDD was positively associated with brooding and negatively related to cognitive reappraisal. Overall, PGS based on both broad and clinical depression phenotypes have modest utility in adult and child samples of depression.

scholarly journals 699 Sleep Health Traits and COVID-19: Mortality Risk from the UK Biobank

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A273-A273
Author(s):  
Xi Zheng ◽  
Ma Cherrysse Ulsa ◽  
Peng Li ◽  
Lei Gao ◽  
Kun Hu
Keyword(s):  
Risk Factors ◽  
Sleep Apnea ◽  
Sleep Duration ◽  
Sex Education ◽  
Mortality Risk ◽  
Self Report ◽  
Severe Illness ◽  
Uk Biobank ◽  
Sleep Health ◽  
The Uk

Abstract Introduction While there is emerging evidence for acute sleep disruption in the aftermath of coronavirus disease 2019 (COVID-19), it is unknown whether sleep traits contribute to mortality risk. In this study, we tested whether earlier-life sleep duration, chronotype, insomnia, napping or sleep apnea were associated with increased 30-day COVID-19 mortality. Methods We included 34,711 participants from the UK Biobank, who presented for COVID-19 testing between March and October 2020 (mean age at diagnosis: 69.4±8.3; range 50.2–84.6). Self-reported sleep duration (less than 6h/6-9h/more than 9h), chronotype (“morning”/”intermediate”/”evening”), daytime dozing (often/rarely), insomnia (often/rarely), napping (often/rarely) and presence of sleep apnea (ICD-10 or self-report) were obtained between 2006 and 2010. Multivariate logistic regression models were used to adjust for age, sex, education, socioeconomic status, and relevant risk factors (BMI, hypertension, diabetes, respiratory diseases, smoking, and alcohol). Results The mean time between sleep measures and COVID-19 testing was 11.6±0.9 years. Overall, 5,066 (14.6%) were positive. In those who were positive, 355 (7.0%) died within 30 days (median = 8) after diagnosis. Long sleepers (>9h vs. 6-9h) [20/103 (19.4%) vs. 300/4,573 (6.6%); OR 2.09, 95% 1.19–3.64, p=0.009), often daytime dozers (OR 1.68, 95% 1.04–2.72, p=0.03), and nappers (OR 1.52, 95% 1.04–2.23, p=0.03) were at greater odds of mortality. Prior diagnosis of sleep apnea also saw a two-fold increased odds (OR 2.07, 95% CI: 1.25–3.44 p=0.005). No associations were seen for short sleepers, chronotype or insomnia with COVID-19 mortality. Conclusion Data across all current waves of infection show that prior sleep traits/disturbances, in particular long sleep duration, daytime dozing, napping and sleep apnea, are associated with increased 30-day mortality after COVID-19, independent of health-related risk factors. While sleep health traits may reflect unmeasured poor health, further work is warranted to examine the exact underlying mechanisms, and to test whether sleep health optimization offers resilience to severe illness from COVID-19. Support (if any) NIH [T32GM007592 and R03AG067985 to L.G. RF1AG059867, RF1AG064312, to K.H.], the BrightFocus Foundation A2020886S to P.L. and the Foundation of Anesthesia Education and Research MRTG-02-15-2020 to L.G.

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