👤 Caroline Faucher

Pathogenic variants in five established leptin-melanocortin pathway genes (LEP, LEPR, MC4R, PCSK1, POMC) are associated with severe early-onset obesity and are targets for emerging treatments. However, these variants are rare in these patients, suggesting the involvement of additional genes interacting with this pathway. Next-generation sequencing (NGS) analysis was performed in 395 patients with severe obesity, including 213 children (mean BMI: 56.3 kg/m Pathogenic heterozygous variants were identified in 34 patients (8.6%), 18 of them harboring pathogenic variants in the 15 additional genes. In adults, early-onset obesity was more frequent in potentially pathogenic variants carriers than in non-carriers (83.3% vs. 55.0%, p = 0.04). No differences were observed in the other phenotypic characteristics. This supports the relevance of expanded genetic testing in severe obesity. Early-onset obesity remains a key clinical feature to guide genetic investigation and identify patients who may benefit from early personalized care and targeted treatments. Show less

BackgroundHabitual daytime napping is a significant aspect of many older adults' sleep-wake cycle. Growing evidence links napping and cognition in the context of Alzheimer's disease (AD), yet little is known about how genetic risk influences this relationship.ObjectiveThis study investigates interactions between genetic risk for AD and napping on cognition in 1655 cognitively healthy middle-aged to older adults.MethodsCognition was assessed using a self-administered online battery and reduced to three variables: memory, visuospatial abilities and executive functions. Genetic risk was assessed with the presence of Show less