Circadian <i>ADCY3</i> Ser107Pro variant bridges difficulty awakening in the morning and adiposity.

ABSTRACT: Modern lifestyles often disturb circadian rhythms, yet the genetic circuits that convert this stress into metabolic dysfunction remain poorly defined. Here, we identify a missense variant in ADCY3 (rs11676272; Ser107Pro) as a pleiotropic regulator of circadian preference and adiposity. Using genome-wide pleiotropy analysis in ∼480,000 UK Biobank participants, we show that the G risk allele (Pro107) increases eveningness, BMI, and fat mass in European (n = 451,324) and African (n = 8,738) ancestry groups, with behavioral amplification by morning difficulty awakening in Europeans and power-limited modeling in other populations. Structural modeling and transcriptomic analysis suggest this allele alters adipose-specific splicing and expression and destabilizes ADCY3 protei

SUBMITTER: Tchio C 

PROVIDER: S-EPMC12860998 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature