ArticleFrontiers in endocrinology2026
Rare endocannabinoid system variants identified by whole-exome sequencing and structural modeling in adults with severe obesity predominantly of childhood onset.
Article in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: The endocannabinoid system (ECS) regulates key processes in energy homeostasis, but its contribution to severe obesity beginning in childhood or adolescence remains incompletely understood. This study aimed to identify rare variants in ECS genes and evaluate their potential structural effects. Methods: A total of 93 adults with severe obesity beginning before 21 years of age (BMI ≥ 35 kg/m²) were recruited from two specialized obesity programs; among participants with onset information, 97.8% reported childhood onset. Whole-exome sequencing was performed, followed by targeted analysis of ECS-related genes. Rare variants (allele frequency <1%) were confirmed by Sanger sequencing and assessed using Results: Nine rare variants were identified in twelve individuals, seven of which were defined as variants of uncertain significance (VUS). Among the observed variants, Conclusions: Rare ECS variants, including a previously unreported
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