Heritability of neonatal acute phase protein levels

Levels of neonatal Acute Phase Proteins (APPs) have been associated with autism and schizophrenia. The relative contributions of genetic and environmental factors to variation in APP levels in the neonatal period are not known. Therefore, we used one of the largest twin samples to date to map the proportions of heritable and non-heritable factors to variations in APPs measured shortly after birth. Moreover, we investigated if any association existed between neonatal APP levels and autism, among monozygotic and dizygotic twins discordant for autism.

Twins were identified and enrolled from registers and a clinical twin study of autism in Sweden. The distributions of APPs measured in dried blood spots taken a few days after birth as part of a national screening program were standardized to reduce any analytical artifacts. The additive genetic (A), common (C) and unique (E) environment components were estimated, using the ACE model, on a sample of 92 twin pairs. We included 61 autism discordant twin pairs for estimating the association between the APPs and autism, using both non-fixed (between) and fixed (within) effects regression models.

For the ACE models, variations in α-2 macroglobulin, C-reactive protein, ferritin, fibrinogen, haptoglobin, serum amyloid A and serum amyloid P were all largely explained by additive genetic factors (70–90 %). Variation in tissue plasminogen activator and procalcitonin were predominantly explained by common environmental factors (60–70 %) with a negligible contribution by genetic factors. Variations in levels of tissue plasminogen activator and procalcitonin in the neonatal period appear to be mainly explained by pregnancy and birth related factors. Variations in levels of other investigated acute phase proteins were largely explained by additive genetic factors. None of the APPs exhibited any significant association with autism in discordant mono- or dizygotic twin pairs. Our findings highlight the importance of considering potential familial confounding in future studies of association between any APP and autism.