Case co-twin study design as a methodology to quantify the effects of life and social adversities: The ImmunoTwin cohort

Life and social adversities experienced before adulthood are decisive drivers of later life health inequalities, which hinge on immune, endocrine and epigenetic changes that reflect an individual’s interaction with the environment. Since monozygotic (MZ) twins share the same genetic background and perinatal environment, they provide a robust approach to identify environmental influences on biological features while controlling genetic confounders. We screened MZ and dizygotic (DZ) twin pairs (aged of 17 to 32 years) from the German TwinLife study for recent and time-distant adversities in their psychosocial environment (PSE). Here, we present three statistical approaches we developed to quantify adverse experiences in 739 twin pairs (349 MZ, 390 DZ). We calculated divergence scores based on score differences between each twin pair. By combining these approaches, we identified adversity-divergent twins (144 MZ, 173 DZ), suggesting that in approximately 41% - 44% of twin pairs, there was a clear divergence in their adversarial experiences and how they interpreted their PSE. Variance modelling suggested that 43% of the adversity experienced by the twins was due to their unique environment, while 23% was from their shared environment while 33% of the variance was explained by genetic factors.