What Twin Studies Tell Us About the Heritability of Brain Development, Morphology, and Function: A Review

The development of brain structure and function shows large inter-individual variation. The extent to which this variation is due to genetic or environmental influences has been investigated in twin studies using structural and functional Magnetic Resonance Imaging (MRI). The current review presents an overview of twin studies using MRI in children, adults and elderly, and focuses on cross-sectional and longitudinal designs. The majority of the investigated brain measures are heritable to a large extent (60–80 %), although spatial differences in heritability are observed as well. Cross-sectional studies suggest that heritability estimates slightly increase from childhood to adulthood. Long-term longitudinal studies are better suited to study developmental changes in heritability, but these studies are limited. Results so far suggest that the heritability of change over time is relatively low or absent, but more studies are needed to confirm these findings. Compared to brain structure, twin studies of brain function are scarce, and show much lower heritability estimates (~40 %). The insights from heritability studies aid our understanding of individual differences in brain structure and function. With the recent start of large genetic MRI consortia, the chance of finding genes that explain the heritability of brain morphology increases. Gene identification may provide insight in biological mechanisms involved in brain processes, which in turn will learn us more about healthy and disturbed brain functioning

Psychiatric Polygenic Risk Scores as Predictor for Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in a Clinical Child and Adolescent Sample

Neurodevelopmental disorders such as attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are highly heritable and influenced by many single nucleotide polymorphisms (SNPs). SNPs can be used to calculate individual polygenic risk scores (PRS) for a disorder. We aim to explore the association between the PRS for ADHD, ASD and for Schizophrenia (SCZ), and ADHD and ASD diagnoses in a clinical child and adolescent population. Based on the most recent genome wide association studies of ADHD, ASD and SCZ, PRS of each disorder were calculated for individuals of a clinical child and adolescent target sample (N = 688) and for adult controls (N = 943). We tested with logistic regression analyses for an association with (1) a single diagnosis of ADHD (N = 280), (2) a single diagnosis of ASD (N = 295), and (3) combining the two diagnoses, thus subjects with either ASD, ADHD or both (N = 688). Our results showed a significant association of the ADHD PRS with ADHD status (OR 1.6, P = 1.39 × 10−07) and with the combined ADHD/ASD status (OR 1.36, P = 1.211 × 10−05), but not with ASD status (OR 1.14, P = 1). No associations for the ASD and SCZ PRS were observed. In sum, the PRS of ADHD is significantly associated with the combined ADHD/ASD status. Yet, this association is primarily driven by ADHD status, suggesting disorder specific genetic effects of the ADHD PRS