Figure 2.

White matter endophenotypes associatedwith genetic risks for schizophrenia and bipolar disorder. A, Map of whitematter volume deficits associated with genetic risks for schizophrenia (redvoxels) and bipolar disorder (blue voxels) superimposed onto a single brainin standard stereotactic space. Green indicates overlapping voxels. Clusterwiseprobability of type 1 error, P =.01 for both schizophreniaand bipolar disorder; that is, <1 false-positive test result. The z coordinate for each axial slice in the plane of the Talairachatlas is given in millimeters, and the right side of each panel representsthe right side of the brain. B, Linear associations between systemic whitematter volume deficits in regions associated with genetic risk for schizophrenia(y-axis) and genetic liability score (x-axis) estimated separately for patientswith schizophrenia, unaffected relatives of patients with schizophrenia, andunaffected relatives of patients with bipolar disorder. First principal componentscores (y-axis) summarize correlated white matter deficits in all regionsfor each individual. C, Linear associations between white matter volume deficitsin the left temporoparietal region identified as endophenotypic for bipolardisorder (y-axis) and genetic liability score (x-axis), estimated separatelyfor patients with bipolar disorder, unaffected relatives of patients withbipolar disorder, and unaffected relatives of patients with schizophrenia.Genetic liability scores are adjusted to the sample mean for age, sex, andsubject group.

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Genetic risk for bipolar disorder was associated with white matter deficitsin the anterior corpus callosum and bilateral frontal, left temporoparietal,and right parietal regions (Figure 2Aand Table 2). All regions of white mattervolume deficit loaded positively for the first PC, which explains 80.7% ofthe total variance. First PC scores were strongly associated with geneticliability, and there was no significant interaction between subject group(patients vs relatives) and genetic liability score (Table 3).

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