Harsh parenting and rs11621961 at the SERPINA6/1 locus: gene-environment interaction effects on hair cortisol in a Brazilian population-based longitudinal study

Hair cortisol concentration (HCC) reflects long-term hypothalamic-pituitary-adrenal (HPA) axis activity and is a biomarker of chronic stress. Although HCC has been linked to mental health, less is known about how genetic susceptibility and early adversity jointly influence cortisol regulation, particularly in low- and middle-income countries (LMICs). This study examined whether harsh parenting predicts adolescent HCC and whether this association is moderated by genetic variation. Data were drawn from 1,823 participants in the 2004 Pelotas (Brazil) Birth Cohort, followed at ages 6, 11, and 15. Genetic data were obtained using the Illumina Global Screening Array v2, and HCC was measured at age 15 using ELISA. Harsh parenting was assessed using the Conflict Tactics Scales: Parent-Child Version, and cumulative exposure was analyzed using linear regression models. Gene-by-environment interaction analyses tested whether rs11621961 moderated the association between harsh parenting and HCC. Greater cumulative exposure to harsh parenting, particularly overall harsh parenting and corporal punishment, was associated with higher HCC at age 15. Evidence of G × E interaction indicated stronger associations among individuals carrying more copies of the T allele, suggesting a gene-dosage effect. These findings highlight how genetic susceptibility may amplify the physiological consequences of early-life stress in LMIC settings.