Distribution of genetic architecture indicates the presence of common neuropathology across brain disorders

The distribution of genetic architecture across the hippocampal formation suggests that common neuropathology exists across brain disorders.

It plays a role in disorders such as autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), bipolar disorder (IPB), and migraine (MIG), and tests of recollection memory show hippocampal dysfunction in major depression (MD).

These studies highlight the importance of hippocampal formation in a variety of psychiatric and neurological disorders that occur throughout the lifespan.

We used FreeSurfer 7.127 to segment the hippocampal formation into 19 subregions and total hippocampus volume (sum of all subfields) from 35,411 genotyped white British individuals (age range: 45–82 years, mean: 64.4 years, s.d.: 7.5 years) (Fig. 1a).

We calculated the average volume between the left and right hemispheres and residualized for age, age squared, sex, scanning site, image quality proxy, intracranial volume, and genetic principal components for each of these.

The residuals were then used in genetic analyses, feeding the entire hippocampus volume into the Multivariate Omnibus Statistical Test (MOSTest), which uses permutation testing to identify genetic effects across multiple phenotypes.