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Associations of GLP-1-related genotypes with appetitive traits, food cue reactivity, and prospective weight gain in pre-adolescence

Award Number: F30DK138711
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2024
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Associations of GLP-1-related genotypes with appetitive traits, food cue reactivity, and prospective weight gain in pre-adolescence - Project Summary Obesity is a chronic disease that is increasingly common, resistant to treatment, and responsible for a broad range of medical comorbidities and excess mortality. Pediatric obesity is especially concerning as it frequently persists throughout life. The causes of obesity involve interactions of genetics and environmental factors. The Behavioral Susceptibility Theory suggests genetic factors predispose individuals to unfavorable appetite regulation such that when they are exposed to highly palatable foods, excess consumption, positive energy imbalance, and weight gain result. Considering obesity polygenic risk scores (PRS) from recent genome-wide association studies, my previous research found obesity PRSs relate to appetitive traits and BMI in children. As a target of recent effective anti-obesity medications, GLP-1 and associated pathways play an important therapeutic role through appetite regulation. However, there is a knowledge gap as to how the endogenous GLP-1 pathway may drive or prevent obesity, specifically how genetic variants associated with this pathway may relate to phenotypes of appetitive traits (observable behaviors) and food cue reactivity (a conditioned reward response to food cues). Specific Aim 1 will incorporate genotype and appetitive trait data collected on a sample of 312 children aged 9-12 years, allowing the association of GLP-1 related genetic variants and appetitive traits to be assessed, both as main effects and in higher order epistatic interactions. This will allow my novel training in methods for high dimensional genetic data analysis. Specific Aim 2 will leverage fMRI data conducted in a subset of 176 of these children to associate these variants independently and interactively with food cue reactivity in reward regions of the brain. This will allow my novel training in the processing and analysis of fMRI data. Finally, linking these characteristics to deleterious weight gain in pre- adolescence, Specific Aim 3 will associate GLP-1 related genetic variants independently and interactively with prospective weight gain in these children. It will further explore how appetitive traits and food cue reactivity may mediate an association between GLP-1 pathway heterogeneity and prospective weight gain. This will allow my novel training in methods for statistical mediation analysis. I will gain further training in the clinical application of obesity research, and professional skills in preparation for an independent career as a physician scientist. This F30 proposal will allow me to contribute to the understanding of causes of obesity through appetitive mechanisms and this increased etiologic understanding may enhance obesity prevention and treatment efforts. The highly collaborative environment at Dartmouth College, Dartmouth Health, and the Quantitative Biomedical Sciences graduate program will help me to achieve my proposed research and training goals.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $55,114 )
2026	2026	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	8/18/2026	NON-COMPETING CONTINUATION	$55,114
														Subtotal = $55,114

Issue Date FY: 2025 ( Subtotal = $54,538 )
2025	2025	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	8/19/2025	NON-COMPETING CONTINUATION	$54,538
														Subtotal = $54,538

Issue Date FY: 2024 ( Subtotal = $53,774 )
2024	2024	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/14/2024	NEW	$53,774
2024	2024	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	8/14/2024	NEW	$0
														Subtotal = $53,774

Grand Total All Awards = $163,426

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Associations of GLP-1-related genotypes with appetitive traits, food cue reactivity, and prospective weight gain in pre-adolescence

Award Number: F30DK138711

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2024

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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