1707-P: Maternal Smoking Around Birth, Offspring Genetic Susceptibility to Adiposity, and Risk of Type 2 Diabetes

Prenatal exposure to maternal smoking (MS) and genetic predisposition to obesity have been related to an increased risk of developing type 2 diabetes (T2D), individually; however, little is known about whether these risk factors may interact with each other. This study included 394867 European participants in UK Biobank. Three types of adiposity polygenetic score (PGS) were created based on 97, 66, and 12 genetic loci associated with BMI, waist-to-hip ratio adjusted for BMI (WHRadjBMI), and percentage of body fat (PBF). The adjusted odds ratio (OR) of MS for T2D was 1.25 (95% CI: 1.21-1.28), and ORs for T2D were 1.09 (1.08-1.11), 1.07 (1.05-1.08), and 1.02 (1.01-1.04) per one SD increment of BMI-, WHRadjBMI-, and PBF- PGS. The joint associations of MS and a higher adiposity genetic susceptibility for T2D were 1.52 (1.45-1.60), 1.43 (1.36-1.50), and 1.35 (1.28-1.41), respectively. The estimated proportions of the joint association were 45.1% for MS alone, 28.4% for genetic susceptibility to obesity alone, and 26.5% for their additive interaction. Our results indicate that the increased risk of T2D due to the joint association of MS and adiposity genetic predisposition was greater than each factor. Our findings extend our knowledge on the synergistic contribution of prenatal factors and genetic make-up to adiposity on T2D risk, and re-emphasize the importance of smoking cessation around pregnancy in women.