Association of maternal smoking during pregnancy with youth depression and subsequent adult chronic diseases in offspring

This study aimed to elucidate the relationship between maternal smoking during pregnancy (MSDP) and the incidence of youth depression, examine the modifying role of genetic susceptibility, and assess subsequent physical health risks in adulthood. We utilized data from 60,839 participants in the UK Biobank. Cox proportional hazards models were applied to evaluate the impact of MSDP on the onset of youth depression. Genome-wide association studies (GWAS) and gene-environment interaction analyses were conducted to identify genetic variants influencing youth depression and their interactions with MSDP. Polygenic risk scores (PRS) were calculated to assess genetic contributions. Multi-state modeling explored health transitions from MSDP exposure to youth depression and 24 chronic physical diseases in adulthood. The GWAS identified 10 significant SNPs within the ABR gene region (P < 5 × 10^-8) associated with youth depression. MSDP was associated with higher risks of youth depression (HR = 1.26, 95% CI: 1.18-1.35), especially among females (HR = 1.34, 95% CI: 1.24-1.45) and participants with high PRS (HR = 2.35, 95% CI: 1.97-2.80). Additionally, MSDP was associated with increased risks of five chronic conditions, including asthma (HR = 1.37, 95% CI: 1.14-1.66), chronic obstructive pulmonary disease (COPD) (HR = 3.53, 95% CI: 2.20-5.65), hypertension(HR = 1.29, 95% CI: 1.12-1.50), liver disease (HR = 1.88, 95% CI: 1.31-2.71), and peripheral vascular disease (HR = 2.33, 95% CI: 1.47-3.71). Notable gender differences in these effects were observed. Overall, MSDP was associated with a greater likelihood of youth depression, especially among females and those with higher genetic susceptibility, and with a higher burden of chronic physical conditions in adulthood. Targeted smoking cessation during pregnancy may therefore yield substantial intergenerational benefits for both mental and physical health.