Schizophrenia and brain volume genetic covariation

Schizophrenia is a heterogeneous group of disorders at the level of genetic etiology and clinical presentation. Disentangling the relationship between genotype and phenotype will help determine which patient features are a cause or consequence of disease. On page 420, Franke et al. took advantage of large-scale genome-wide association studies of schizophrenia and of subcortical brain volumes to examine the relationship between the two.

There was no genetic overlap between the overall common variants influencing both sets of traits (see picture for genetic overlap between schizophrenia and hippocampal volume), nor did they share any single risk gene. Thus, even though meta-analyses find subcortical volumetric differences in schizophrenia patients, it is unlikely these are due to genetic risk factors driving the disease. The authors also found that the effect sizes of variants influencing disease risk were similar to those influencing brain volumes. This is in line with previous evidence that brain measures are not genetically simpler but rather are just as complex as behavioral measures such as psychiatric diagnosis.

Large-scale studies of additional structural and functional imaging measures in patients and controls are needed to determine, in vivo, the brain circuits and processes mediating the effect of genetic risk for schizophrenia.