Maternal smoking, genetic susceptibility, and birth-to-adulthood body weight

Maternal smoking (MS) is associated with low birthweight (BW) but adult obesity in offspring, however, it remains unknown whether it modifies offspring's genetic susceptibility to obesity on BW, adult body weight, and birth-to-adulthood body weight tracking pattern.

This study included 246,759 UK Biobank participants with information on MS, BW (kg), adult body weight and BMI (kg/m²). Individual polygenetic score (PGS) was created on the basis of 97 BMI-associated genetic loci. We calculated individual birth-to-adulthood percentile change, and body weight tracking patterns that combined BW levels (<2.5, 2.5-4.0, and ≥4.0 as low, normal and high BW [LBW, NBW, and HBW]) and adulthood obesity status (≥30 as obesity [OB] and <30 as non-obesity [NOB]), including LBW-to-OB, LBW-to-NOB, NBW-to-OB, NBW-to-NOB, HBW-to-OB, and HBW-to-NOB.

Participants exposed to MS had a 0.108 kg lower BW (95% CI, -0.114 to -0.102), a 1.418 kg higher adult body weight (95% CI, 1.291-1.545), and a 6.91 greater percentile increase of body weight from birth to adulthood (95% CI, 6.62-7.21), compared with those nonexposed (all P < 0.001). In comparison to participants of NBW-to-NOB, MS was associated with an approximately twofold higher risk of LBW-to-OB (odds ratio [OR] 1.98, 95% CI 1.87-2.10), and a reduced likelihood of HBW-to-NOB (0.85, 95% CI 0.82-0.88). The increases in BW, adult body weight, and birth-to-adulthood percentile change per increment of 10 BMI-PGS were 0.021 vs. 0.012, 2.50 vs. 2.11, and 4.03 vs. 3.55, respectively, for participants exposed vs. nonexposed to MS (all P_interaction < 0.05).

Our results indicate that exposure to MS is associated with an increased risk of transition from low BW-to-adulthood obesity, and reduced likelihood of change from high BW-to-normal adult body weight. MS may modify the relation of genetic susceptibility to obesity and body weight in offspring.