Oligogenic inheritance in severe adult obesity.

BACKGROUND/OBJECTIVE: The genetic architecture of extreme non-syndromic obesity in adults remains to be elucidated. A range of genes are known to cause monogenic obesity, but even when pathogenic mutations are present, there may be variable penetrance. METHODS: Whole-exome sequencing (WES) was carried out on a 15-year-old male proband of Pakistani ancestry who had severe obesity. This was followed by family segregation analysis, using Sanger sequencing. We also undertook re-analysis of WES data from 91 unrelated adults with severe obesity (86% white European ancestry) from the Personalised Medicine for Morbid Obesity (PMMO) cohort, recruited from the UK National Health Service. RESULTS: We identified an oligogenic mode of inheritance of obesity in the proband's family-this provided the impetus to reanalyze existing sequence data in a separate dataset. Analysis of PMMO participant data revealed two further patients who carried more than one rare, predicted-deleterious mutation in a known monogenic obesity gene. In all three cases, the genes involved had known autosomal dominant inheritance, with incomplete penetrance. CONCLUSION: Oligogenic inheritance may explain some of the variable penetrance in Mendelian forms of obesity. We caution clinicians and researchers to avoid confining sequence analysis to individual genes and, in particular, not to stop looking when the first potentially-causative mutation is found.

Do mobile phone surfaces carry SARS-CoV-2 virus? A systematic review warranting the inclusion of a "6th" moment of hand hygiene in healthcare.

BACKGROUND: Mobile phones, used in billions throughout the world, are high-touch devices subject to a dynamic contamination of microorganisms and rarely considered as an important fomite to sanitise systematically. The emergence of SARS-CoV-2 resulted in the COVID-19 pandemic, arguably the most impactful pandemic of the 21st century with millions of deaths and disruption of all facets of modern life globally. AIM: To perform a systematic review of the literature exploring SARS-CoV-2 presence as a contaminant on mobile phones. METHODS: A systematic search (PubMed and Google Scholar) of literature was undertaken from December 2019 to March 2023 identifying English language studies. Studies included in this review specifically identified or tested for the contamination of the SARS-CoV-2 virus or genome on mobile phones while studies testing for SARS-COV-2 in environments and/or other fomites samples than but not mobile phones were excluded. RESULTS: A total of 15 studies with reports of SARS-CoV-2 contamination on mobile phones between 2020 and 2023 were included. Amongst all studies, which encompassed ten countries, 511 mobile phones were evaluated for the presence of SARS-CoV-2 contamination and 45% (231/511) were positive for SARS-CoV-2. All studies were conducted in the hospital setting and two studies performed additional testing in residential isolation rooms and a patient's house. Four studies (3 in 2020 and one in 2021) reported 0% contamination while two other studies (in 2020 and 2022) reported 100% of mobile phone contamination with SARS-COV-2. All other studies report mobile phones positive for the virus within a range of 4-77%. CONCLUSION: A total of 45% of mobile phones are contaminated with SARS-CoV-2 virus. These devices might be an important fomite vector for viral dissemination worldwide. Competent health authorities are advised/recommended to start a global implementation of mobile phone decontamination by introducing regulations and protocols in public health and health care settings such as the 6th moment of hand washing.

Higher Waist Hip Ratio Genetic Risk Score Is Associated with Reduced Weight Loss in Patients with Severe Obesity Completing a Meal Replacement Programme.

Background: A better understanding of the influence of genetic factors on the response to lifestyle interventions in people with obesity may allow the development of more personalised, effective and efficient therapeutic strategies. We sought to determine the influence of six obesity-related genetic risk scores on the magnitude of weight lost by patients with severe obesity who completed a dietary intervention. Methods: In this single-centre prospective cohort study, participants with severe and complicated obesity who completed a 24-week, milk-based meal replacement programme were genotyped to detect the frequency of common risk alleles for obesity and type 2 diabetes-related traits. Genetic risk scores (GRS) for six of these traits were derived. Participants with a potentially deleterious monogenic gene variant were excluded from the analysis. Results: In 93 patients completing the programme who were not carrying a known obesity-related gene mutation, 35.5% had diabetes, 53.8% were female, mean age was 51.4 ± 11 years, mean body mass index was 51.5 ± 8.7 and mean total weight loss percent at 24 weeks was 16 ± 6.3%. The waist-hip ratio (WHR) GRS was inversely associated with percentage total weight loss at 24 weeks (adjusted ß for one standard deviation increase in WHR GRS -11.6 [-23.0, -0.3], p = 0.045), and patients in the lowest tertile of WHR GRS lost more weight. Conclusions: Patients with severe and complicated obesity with a genetic predisposition to central fat accumulation had less weight loss in a 24-week milk-based meal replacement programme, but there was no evidence for influence from the five other obesity-related genetic risk scores on the response to dietary restriction.