(OR31-05-24) Obesity Genetic Risk Scores and Weight Loss in Participants From the Daily Caloric Restriction Versus Intermittent Fasting Trial (DRIFT)

Tuesday, July 2, 2024

8:48 AM – 9:00 AM CT

Location: W184

Presenting Author(s)

Emily N. Yeo, MS (she/her/hers)

PhD Student
University of Colorado Boulder
Boulder, Colorado, United States

Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

Co-Author(s)

AS

Ashley W. Scadden

University of Colorado Anschutz, United States
Joanne B. Cole, PhD

Assistant Professor
University of Colorado School of Medicine
Aurora, Colorado, United States
ZP

Zhaoxing Pan

University of Colorado Anschutz, United States
Sarah Borengasser, PhD, MS (she/her/hers)

Associate Professor
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
KJ

Kristen L. James

University of Colorado Anschutz, United States
DB

Daniel Bessesen, MD

University of Colorado
Aurora, Colorado, United States
VC

Victoria A. Catenacci

University of Colorado Anschutz, United States
EL

Elizabeth M. Litowski

University of Michigan, United States
PM

Paul Maclean, PhD

University of Colorado
Aurora, Colorado, United States
EM

Edward L. Melanson

University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States
DO

Danielle Ostendorf, PhD

University of Colorado
Aurora, Colorado, United States
CL

Cathy Lozupone

University of Colorado Boulder, United States
MS

Maggie A. Stamislawski

University of Colorado Anschutz, Colorado, United States

Objectives: Global obesity rates and severity continue to rise, emphasizing the need to understand the determinants of weight loss and maintenance. Given that genetic factors may influence responsiveness to weight loss efforts, we aimed to examine the associations of obesity genetic risk scores (GRS) to weight loss over a one-year behavioral weight loss intervention, the Daily caloric Restriction versus Intermittent Fasting Trial (DRIFT).

Methods: Participant information was collected at baseline, 6, and 12-months. Obesity GRS were calculated based on 95 genetic variants for 66 participants, genotyped using the Illumina Infinium Multi-Ethnic Global Array. We used linear regression models to assess the relationship between high or low obesity GRS, defined as above or below the median GRS, and percentage weight loss from baseline weight, during baseline to 6-months and 6 to 12-months intervals, adjusting for age, sex, study cohort, and dietary intervention group.

Results: Individuals with high obesity GRS (n=31) achieved significantly (p = 0.019) greater weight loss from baseline to 6-months (mean (sd) = -9.3 (5.4) %) compared to participants with low obesity GRS (n=28; mean (sd) = -7.1 (5.1) %). The opposite pattern was observed during the subsequent 6 to 12-month study period (p = 0.004); on average, individuals with high GRS experienced weight gain (mean (sd) = 0.4 (3.3) %), whereas participants with low obesity GRS continued to lose weight (mean (sd) = -1.1 (4.5) %).

Conclusions: These results indicate individuals with elevated obesity GRS presented greater weight loss during the initial phase of a dietary weight loss intervention but were more susceptible to weight regain than participants with low obesity GRS during the last 6-months of the intervention. Although insightful, the modest sample size of this analysis underscores the imperative for future investigations with larger cohorts, enabling a more robust exploration of the links between genetic susceptibility to obesity and the propensity to achieve and maintain successful weight loss.

Funding Sources: NIH K01 HL157658 (M.A.S.), R01 DK111622 (V.A.C.), Curci Fellowship (E.Y) and F32 DK122652 (D.M.O.), American Heart Association 18IPA34170317 (S.J.B.), Colorado Nutrition & Obesity Research Center P30 DK048520, and Colorado Clinical & Translational Sciences Institute Colorado CTSA Grant Number UL1 TR002535.