Associations of maternal CDKAL1 gene with adverse offspring growth patterns.

OBJECTIVE

To explore the association between maternal cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) gene and adverse growth patterns in offspring aged 1-8 years, and whether gestational diabetes mellitus (GDM) mediates this association.

METHODS

An 8-year follow-up was conducted on 345 mother-infant pairs in Tianjin, China. Growth patterns in offspring aged 1-8 years were identified by group-based trajectory modeling. Logistic regression and restricted cubic splines analyzed the association between CDKAL1 polygenic risk scores (PRS) and growth patterns in offspring aged 1-8 years.

RESULTS

Four growth patterns were identified, including normal (n = 151), persistent lean (n = 128), and obesity (n = 66), which included both late and persistent obesity subtypes. In the adjusted model, the CDKAL1 PRS > 0.5 was associated with the persistent lean growth pattern (OR: 1.91, 95%CIs: 1.32-2.77) and the obesity growth pattern (OR: 2.07, 95% CIs: 1.65-2.60). After further adjustment for GDM, the associations remained significant for both the persistent lean growth pattern (OR: 1.97, 95% CI: 1.36-2.85) and the obesity growth pattern (OR: 2.19, 95% CI: 1.74-2.75).

CONCLUSION

Maternal CDKAL1 gene was associated with adverse growth patterns in offspring, independently of GDM.

IMPACT: Maternal CDKAL1 gene independently increases offspring's dual risk of persistent lean and obese growth patterns during childhood, independently of gestational diabetes (GDM). Challenges conventional understanding by revealing a direct effect of maternal genes on offspring growth beyond GDM-mediated pathways. Shifts research focus toward GDM-independent mechanisms, such as placental programming or direct metabolic set-point regulation. Enables early stratification of childhood growth risks and facilitates preemptive personalized nutritional interventions. Provides novel genetic perspectives and preventive opportunities for addressing the dual burden of childhood growth disparities.