The COMT (rs4680) gene is associated with differential susceptibility to beneficial and adverse environments. Carriers of the COMT GG-genotype have been reported to have poorly regulated impulses, but improved impulse-control under conditions of stress (e.g. ‘warriors’). In adults, carriers of the COMT GG-genotype, or 'warriors' have increased risk for obesity, possibly from interactions with obesogenic environments, but risks resulting from in-utero susceptibility have not been investigated. We examine the risk of macrosomia among 'warriors' born to mothers with, and without gestational diabetes mellitus (GDM), an adverse in-utero environment known to increase the risk of macrosomia.


Mothers were recruited to participate in the Tianjin GDM Observational Study, conducted between 2005 and 2009. This study includes 1087 mother-child pairs with GDM diagnostic tests, and with available data on pregnancy outcomes, genetic profiles, and sociodemographic factors collected in a survey administered post-partum. Odds of macrosomia were estimated using logistic regression tests, stratified by GDM status. All models adjusted for child sex, gestational age, maternal age, income, and maternal smoking habits.


Of the 545 GDM cases vs. 542 non-GDM controls, 175 children were born with macrosomia (111 to mothers with GDM, p<0.001). The COMT GG-genotype was associated with lower odds of macrosomia (OR=0.65, p=0.014). After stratification by GDM status, lower odds of macrosomia were associated with the GG-genotype (OR=0.62, p=0.037) among children born to mothers with GDM, but no gene-environment interaction was found among children born to mothers without GDM (OR=0.65, p=0.159).


Differential susceptibility to obesogenic environments may be present in the womb. Results suggest GDM may introduce “stress-like” conditions in-utero that trigger a protective effect against macrosomia among carriers of the COMT GG-genotype. In utero gene-environment interactions merit further investigations.