The psychosocial aspects of obesity: a quantitative & qualitative study

This Health Services Research PhD, funded by the Chief Scientist Office (CSO), investigated the psychosocial aspects of obesity in a community sample of men and women aged 30-60 living in deprived and affluent areas of Greater Glasgow. The study incorporated a mixed method design and combined a community health survey and semi-structured interviews with a purposively selected sub-sample of questionnaire respondents. 52% of the participants who completed the questionnaire were either overweight or obese and 16% were defined as obese. Obesity and body image were not significant predictors of poor psychological health. Furthermore, low self-esteem was the most significant predictor of poor psychological health for both men and women. The quantitative and qualitative findings demonstrate that obese individuals are aware of their current weight status and express a desire to lose weight. Potential motivating factors for weight loss included health concerns, appearance, special occasions and psychological factors such as increased self-esteem and self-confidence. Participants were knowledgeable about the causes of obesity and had absorbed and understood health promotion messages regarding healthy eating and physical activity. However, they identified a number of barriers, which prevented them from fully implementing health promotion advice. The qualitative findings suggest the possibility of a cyclical relationship between dieting depression and emotional eating. In addition, the findings demonstrate that weight cycling – losing and regaining weight – was a common experience for the interviewees. As weight cycling is a potentially damaging health problem, it might be more appropriate to encourage obese individuals to maintain a stable weight and improve their health by re-focusing the issue on fitness rather than fatness

Experiences of binge eating among clients attending a weight management service

Objectives: Binge Eating Disorder (BED) is prevalent in individuals with morbid obesity and it can impact on weight loss treatment outcomes. This study used Leventhal's selfregulatory model of illness behaviour as a framework for eight semi-structured interviews in order to gain an insight into participants' experiences of obesity and binge eating. Design: Interpretative Phenomenological Analysis (IP A) was used to explore participants' experiences of obesity and binge eating in a small sample of participants attending a weight managment service. Methods: Semi-structured interviews were conducted with eight participants who had BED and were attending a specialist weight management service for weight loss treatment. The interview transcripts were analysed using IPA. Results: Two superordinate themes emerged from the analysis and an analytic narrative was constructed under the headings 'struggle with weight loss' and 'standing in the way of control.' The concept of control was central to both of the emergent themes as the participants perceived a lack of control over their eating and their ability to lose weight. Conclusions: The results revealed that there was a complex and cyclical relationship between weight loss attempts and binge eating. A number of implications for clinical practice and future research are outlined

Stratified analyses refine association between TLR7 rare variants and severe COVID-19

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (<60 years) cases with no reported clinical risk factors (n = 378), compared to 0.24% of controls (odds ratio [OR] = 12.3, p = 1.27 × 10−10). Incorporation of the results of either functional assays or protein modeling led to a pronounced increase in effect size (ORmax = 46.5, p = 1.74 × 10−15). Association signals for the X-chromosomal gene TLR7 were also detected in the female-only subgroup, suggesting the existence of additional mechanisms beyond X-linked recessive inheritance in males. Additionally, supporting evidence was generated for a contribution to severe COVID-19 of the previously implicated genes IFNAR2, IFIH1, and TBK1. Our results refine the genetic contribution of rare TLR7 variants to severe COVID-19 and strengthen evidence for the etiological relevance of genes in the interferon signaling pathway

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease