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 β 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.