Leveraging Genomic Associations in Precision Digital Care for Weight Loss: Cohort Study (Preprint)

Abstract

BACKGROUND In this age of global COVID-19 pandemic, the urgency of addressing an epidemic of obesity and associated inflammatory illnesses has come to the fore. Studies have demonstrated that interactions between single nucleotide polymorphisms (SNPs) and lifestyle interventions like food and exercise may vary metabolic outcomes, contributing to obesity and therapeutic response. However, there is a paucity of research relating outcomes from digital therapeutics to inclusion of genetic data in care interventions. OBJECTIVE This study aims to describe and model weight loss of subjects enrolled in a precision digital weight loss program informed by machine learning analysis of subject data, including genomic. It was hypothesized that weight loss models would exhibit better fit when incorporating genomic data than utilizing demographic and engagement variables alone. METHODS A cohort of 393 participants enrolled in Digbi Health’s personalized digital care program for 120 days was analyzed retrospectively. Care protocol included the use of subject genomic and gut microbiome data informing precision coaching by mobile app and personal coach. Two linear regression models of weight loss in this cohort (pounds lost, percentage lost) as a function of demographic and behavioral engagement variables were fit. Genomic-enhanced models were built by adding 197 SNPs from subject genomic data as predictors, then refitting, employing Lasso regression on SNPs for variable selection. Success/failure logistic regression models were also fit, with and without genomic data. RESULTS 72% of subjects in this cohort lost weight, while 17% maintained stable weight. 142 subjects lost 5% within 120 days. Models describe the impact of demographic and clinical factors, behavioral engagement, and genomic risk on weight loss. The addition of genomic predictors improved the mean squared error of weight loss models (pounds lost and percent) from 70 to 60 and 16 to 13 respectively. The logistic model improved pseudo R2 from 0.193 to 0.285. Gender, engagement and specific SNPs were significantly associated with weight loss. SNPs within genes involved in metabolic pathways that process food and regulate storage of fat were associated with weight loss in this cohort. This included rs17300539_G (insulin resistance, monounsaturated fat metabolism), rs2016520_C (BMI, waist circumference, cholesterol metabolism), and rs4074995_A (calcium-potassium transport, serum calcium levels). Models described greater average weight loss for subjects having more of these risk alleles. Notably, coaching for dietary modification was personalized to these genetic risks. CONCLUSIONS Adding genomic information in modeling outcomes of a digital precision weight loss program greatly enhanced model accuracy. Interpretable weight loss models pointed to efficacy of coaching informed by subjects’ genomic risk, accompanied by active engagement of subjects in their own success. While large-scale validation is needed, our study preliminarily supports precision dietary interventions for weight loss utilizing genetic risk, with digitally delivered recommendations alongside health-coaching to improve intervention efficacy.