Nature genetics · 2026
Genome-wide mapping of common and rare variant effects on adiposity across childhood.
СтатьяНазвание и аннотация: Перевод в очереди
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Kentistou Katherine A, Sundfjord Jonas, Karimi Roya, Kaisinger Lena R, Hofmeister Robin J, Fragoso-Bargas Nicolas, Lupu Adina E, Zhao Yajie, Tadross John A, Steuernagel Lukas, Dowsett Georgina K C, Lockhart Sam, Brüning Jens C, Liu Jimmy, Cortes Adrian, Lo Yancy, Davitte Jonathan, Clement Lieven, Havdahl Alexandra, Andreassen Ole A, Bratland Eirik, Lam Brian Y H, O'Rahilly Stephen, Yeo Giles S H, Njølstad Pål R, Kutalik Zoltán, Day Felix R, Vaudel Marc, Perry John R B, Ong Ken K, Johansson Stefan
Аннотация
Our understanding of the genetic architecture of obesity is primarily based on studies of adults, with sparser data from childhood. Here, we conducted age-stratified genetic association studies against objectively measured (n = 62,276) or recalled childhood adiposity-related traits (neff = 599,924), identifying 624 common variants associated with childhood adiposity, with one-third having no concordant association with adult body mass index. Signals linked to the leptin-melanocortin pathway (BSX, GNAS, LEPR and PCSK1) and incretin signaling (GIPR and GLP1R) showed childhood-specific effects on adiposity. Single-nucleus RNA sequencing data identified childhood-specific adiposity-regulating cell populations in the arcuate nucleus and mammillary bodies, indicating neurocircuits that regulate adiposity specifically during childhood. Finally, sequencing in 479,615 individuals uncovered rare protein-coding variation in ADCY3, CALCR, MC4R, MRAP2, POMC and MYH13, exhibiting stronger associations in childhood than in adults. Our findings suggest that childhood provides a more sensitive window for the study of key endocrine and neuropeptide pathways that regulate energy balance.