678 research outputs found
Diving deep—multipronged investigations into RIPK1 as a risk factor for obesity
No full textA recent study by Karunakaran et al. has suggested RIPK1 is important in obesity and related metabolic traits. With genetic variation associated with expression and the risk of obesity, and repression of activity leading to a favorable metabolic profile in an obesogenic model, is there evidence for a potential therapeutic role
Inflammation, insulin resistance and components of the metabolic syndrome : Mendelian randomisation as a tool for the dissection of epidemiological relationships : has the pawn risen too early?
No full textEThOS - Electronic Theses Online ServiceGBUnited Kingdo
Commentary:One size fits all: are there standard rules for the use of genetic instruments in Mendelian randomization?
No full text[no abstract
Merseyside Violence Reduction Partnership Whole System Evaluation Report: 2022-23
No full textMerseyside is one of several areas allocated funding since 2019 by the UK government to establish a Violence Reduction Unit. To inform the continued development of the Merseyside Violence Reduction Partnership (MVRP) since November 2019, Liverpool John Moores University (LJMU), have been commissioned to evaluate the MVRP as a whole (Quigg et al, 2020, 2021, 2022), and selected work programmes. In addition, since 2022/23, LJMU have been commissioned to implement additional research to fill gaps in local knowledge. This report forms one of a suite of outputs from the 2022/23 evaluation work programme, and specifically presents a whole system evaluation of the MVRP. Additional evaluation reports for 2022/23 explore: The Mentors in Violence Prevention Programme (Butler et al, 2023). Merseyside Police Trauma Informed Training (Wilson et al, 2023). The Navigator Programme (Harris et al, 2023). Ariel Trust Violence Reduction school education programmes (Butler et al, 2023). Child/young person violence and abuse towards a parent/carer (Bates et al, 2023). Time Matters (Harris et al, 2023). The Nurturing Programme at HMP Altcourse (to be published December 2023). Evaluation outputs are available on the MVRP website: www.merseysidevrp.com or via the author
The UK Biobank:A Shining Example of Genome-Wide Association Study Science with the Power to Detect the Murky Complications of Real-World Epidemiology
No full textGenome-wide association studies (GWAS) studies have successfully identified thousands of genetic variants reliably associated with human traits. Albeit restricted to certain variant frequencies, this has led to an improvement in our understanding of the genetic architecture of complex traits and diseases. The availability of large genomic biobanks such as the UK Biobank (UKBB) study have brought substantial analytical power to association studies. The dramatic expansion of GWAS sample sizes improves power of estimation of effect sizes, genomic prediction and the potential for applied analyses such as those relating to causal inference. However, in the same moment, the availability of substantial analytical power and enabling analytical capacity can increase the complications and inferential complexity associated with GWAS and other applied analyses. In this review, we discuss the revolutionary impact that UKBB has had in the GWAS era and some of the opportunities and challenges of using data from this world-leading study.<br/
The Genetic Sphygmomanometer: an argument for routine genome-wide genotyping in the population and a new view on its use to inform clinical practice.
No full textInitial genomewide association studies were exceptional owing to an ability to yield novel and reliable evidence for heritable contributions to complex disease and phenotype. However the top results alone were certainly not responsible for a wave of new predictive tools. Despite this, even studies small by contemporary standards were able to provide estimates of the relative contribution of all recorded genetic variants to outcome. Sparking efforts to quantify heritability, these results also provided the material for genomewide prediction. A fantastic growth in the performance of human genetic studies has only served to improve the potential of these complex, but potentially informative predictors. Prompted by these conditions and recent work, this letter explores the likely utility of these predictors, considers how clinical practice might be altered through their use, how to measure the efficacy of this and some of the potential ethical issues involved. Ultimately we suggest that for common genetic variation at least, the future should contain an acceptance of complexity in genetic architecture and the possibility of useful prediction even if only to shift the way we interact with clinical service providers
Genetic influences on trajectories of systolic blood pressure across childhood and adolescence
No full textBACKGROUND: Blood pressure (BP) tends to increase across childhood and adolescence, but the genetic influences on rates of BP change are not known. Potentially important genetic influences could include genetic variants identified in genome-wide association studies of adults as being associated with BP, height, and body mass index. Understanding the contribution of these genetic variants to changes in BP across childhood and adolescence could yield understanding into the life course development of cardiovascular risk. METHODS AND RESULTS: Pooling data from 2 cohorts (the Avon Longitudinal Study of Parents and Children [n=7013] and the Western Australian Pregnancy Cohort [n=1459]), we examined the associations of allelic scores of 29 single-nucleotide polymorphisms (SNPs) for adult BP, 180 height SNPs, and 32 body mass index SNPs, with trajectories of systolic BP (SBP) from 6 to 17 years of age, using linear spline multilevel models. The allelic scores of BP and body mass index SNPs were associated with SBP at 6 years of age (per-allele effect sizes, 0.097 mm Hg [SE, 0.039 mm Hg] and 0.107 mm Hg [SE, 0.037 mm Hg]); associations with age-related changes in SBP between 6 and 17 years of age were of small magnitude and imprecisely estimated. The allelic score of height SNPs was only weakly associated with SBP changes. No sex or cohort differences in genetic effects were observed. CONCLUSIONS: Allelic scores of BP and body mass index SNPs demonstrated associations with SBP at 6 years of age with a similar magnitude but were not strongly associated with changes in SBP with age between 6 and 17 years. Further work is required to identify variants associated with changes with age in BP.Laura D. Howe, Priyakumari G. Parmar, Lavinia Paternoster, Nicole M. Warrington, John P. Kemp, Laurent Briollais, John P. Newnham, Nicholas J. Timpson, George Davey Smith, Susan M. Ring, David M. Evans, Kate Tilling, Craig E. Pennell, Lawrie J. Beilin, Lyle J. Palmer and Debbie A. Lawlo
Genomic analysis of male puberty timing highlights shared genetic basis with hair colour and lifespan
No full textPublished online: 24 March 2020The timing of puberty is highly variable and is associated with long-term health outcomes. To date, understanding of the genetic control of puberty timing is based largely on studies in women. Here, we report a multi-trait genome-wide association study for male puberty timing with an effective sample size of 205,354 men. We find moderately strong genomic correlation in puberty timing between sexes (rg = 0.68) and identify 76 independent signals for male puberty timing. Implicated mechanisms include an unexpected link between puberty timing and natural hair colour, possibly reflecting common effects of pituitary hormones on puberty and pigmentation. Earlier male puberty timing is genetically correlated with several adverse health outcomes and Mendelian randomization analyses show a genetic association between male puberty timing and shorter lifespan. These findings highlight the relationships between puberty timing and health outcomes, and demonstrate the value of genetic studies of puberty timing in both sexes.Ben Hollis, Felix R. Day, Alexander S. Busch, Deborah J. Thompson, Ana Luiza G. Soares, Paul R.H.J. Timmers, Alex Kwong, Doug F. Easton, Peter K. Joshi, Nicholas J. Timpson, The PRACTICAL Consortium, 23andMe Research Team, Ken K. Ong and John R.B. Perry. Australian Prostate Cancer BioResource (APCB): Wayne Tilley ... Lisa Butler ... Pamela Saunders ... et al
Inflammation proteomic profiling of psychosis in young adults: Findings from the ALSPAC birth cohort
No full textPsychotic disorder is associated with altered levels of various inflammatory markers in blood, but existing studies have typically focused on a few selected biomarkers, have not examined specific symptom domains notably negative symptoms, and are based on individuals with established/chronic illness. Based on data from young people aged 24 years from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK birth cohort, we have examined the associations of 67 plasma immune/inflammatory proteins assayed using the Olink Target 96 Inflammation panel with psychotic disorder, positive (any psychotic experiences and definite psychotic experiences) and negative symptoms, using linear models with empirical Bayes estimation. The analyses included between 2317 and 2854 individuals. After adjustment for age, sex, body mass index and smoking and correction for multiple testing, positive symptoms and psychotic disorder were consistently associated with upregulation of CDCP1 and IL-6, and psychotic disorder was additionally associated with upregulation of MMP-10. Negative symptoms were associated with upregulation of CDCP1 and TRAIL. CDCP1 and MMP-10 are novel markers of psychosis identified in this study, and are involved in immune regulation, immune cell activation/migration, blood-brain barrier disruption, and extracellular matrix abnormalities. Our findings highlight psychosis symptom domains have overlapping and distinct immune associations, and support a role of inflammation and immune dysfunction in the pathogenesis of psychosis
The Genetic Sphygmomanometer: an argument for routine genome-wide genotyping in the population and a new view on its use to inform clinical practice.
No full textInitial genomewide association studies were exceptional owing to an ability to yield novel and reliable evidence for heritable contributions to complex disease and phenotype. However the top results alone were certainly not responsible for a wave of new predictive tools. Despite this, even studies small by contemporary standards were able to provide estimates of the relative contribution of all recorded genetic variants to outcome. Sparking efforts to quantify heritability, these results also provided the material for genomewide prediction. A fantastic growth in the performance of human genetic studies has only served to improve the potential of these complex, but potentially informative predictors. Prompted by these conditions and recent work, this letter explores the likely utility of these predictors, considers how clinical practice might be altered through their use, how to measure the efficacy of this and some of the potential ethical issues involved. Ultimately we suggest that for common genetic variation at least, the future should contain an acceptance of complexity in genetic architecture and the possibility of useful prediction even if only to shift the way we interact with clinical service providers
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