Phenotypic and genetic correlations between diagnosed neurodevelopmental and internalizing disorders

BACKGOUND: Neurodevelopmental disorders (NDDs) such as ADHD, Intellectual Disability (ID), and Autism Spectrum Disorders (ASD), with onset in childhood, have been thoroughly researched with regards to phenotypic and genetic... [ view full abstract ]

BACKGOUND: Neurodevelopmental disorders (NDDs) such as ADHD, Intellectual Disability (ID), and Autism Spectrum Disorders (ASD), with onset in childhood, have been thoroughly researched with regards to phenotypic and genetic overlaps. Similarly, internalizing disorders such as anxiety, depression, and phobias, with onset in adolescence/adulthood, although not as thoroughly, has been assessed for overlaps. Research efforts have been made both for symptom-level data and diagnoses within the disorder groups. Although the disorder spectrums are associated, e.g. by NDDs later developing into internalizing disorders, to our knowledge, no previous study has used family-relation data to specifically investigate the phenotypic, genetic, and environmental overlap between NDD and internalizing disorder spectrums.

Therefore, we estimated the phenotypic and genetic associations between NDDs (ADHD, ASD and ID) and internalizing disorders (anxiety, depression, and phobias) using clinical diagnoses and familial relations in the Swedish population.

METHOD: In a cohort born 1982 through 1996 (N=1,456,683) we identified individuals with and without observed diagnoses in the Swedish National Patient Register. We used the Swedish Twin Register and Multi-Generation Register to identify siblings (MZ and DZ twins, full- and half-siblings). Using the liability-threshold model we then proceeded to estimate the phenotypic (tetrachoric) correlation between all disorders, and the genetic and environmental correlations between all disorders.

RESULTS: The phenotypic correlations, within individuals between disorders, ranged between 0.47 and 0.64 within NDDs and between 0.64 and 0.74 within internalizing disorders. Between NDDs and internalizing disorders correlations ranged from 0.15 to 0.52. Additive genetics explained between 57% and 83% of the correlations between NDDs, between 33% and 55% between internalizing disorders, and between 60% and 100% between NDDs and internalizing disorders. Additive genetic correlations were weaker, 0.53 to 0.69, within NDDs than within internalizing disorders, 0.87 to 1.00, and similar in strength between internalizing disorders and NDDs as within NDDs, 0.24 to 0.85.