AbstractIntroductionGenetic factors contribute to weight gain, but how these effects change over adulthood is still unknown. We studied the impact of genetics on BMI change from young adulthood to old age and its relationship with BMI in early young adulthood.Data and MethodsData from 16 longitudinal twin cohorts, including 111,370 adults (56% women) and 55,657 complete twin pairs (42% monozygotic), were pooled. The data were divided into three stages (young adulthood-early middle age, late middle age, and old age). BMI change was calculated using linear mixed effects and delta slope methods. Genetic and environmental contributions to these changes and their correlations with baseline BMI were estimated through structural equation modeling.ResultsThe average BMI increase per year was 0.18 kg/m² in men and 0.15 kg/m² in women during young adulthood-early middle age (18–50 years), decreasing to ≤0.07 kg/m² at older ages. Genetic effects contributed to BMI change during young adulthood-early middle age (men a²=0.29; women a²=0.26) and less so in late middle age (51–64 years) (men a²=0.05; women a²= 0.16) and old age (>65 years) (men a²=0.13; women a²= 0.18). Most variation was explained by non-shared environmental effects. In men, greater BMI during early young adulthood (18–30 years) was associated with lower BMI change later in life (r= –0.22 to –0.13), and the association was driven by genetic (rA=–0.27) and non-shared environmental (rE=–0.22 to –0.14) factors. In contrast, the association was positive in women (r=0.05–0.28) and was explained by genetic factors (rA=0.27– 0.51).ConclusionGenetics influence BMI change across adulthood, with their impact varying by age and sex. Environmental factors are the main drivers of adult BMI change, highlighting the role of modifiable factors in long-term weight regulation.