Quick Take: Association of a Schizophrenia-Risk Nonsynonymous Variant With Putamen Volume in Adolescents A Voxelwise and Genome-Wide Association Study

Deviations from normal brain development may be implicated in certain psychiatric disorders, including schizophrenia. In this cohort study, investigators obtained genotype data and brain images from 1721 healthy adolescents, 157 patients with schizophrenia, and 149 unaffected siblings of patients in order to identify potential genes and brain structural changes associated with schizophrenia. Using a discovery cohort of healthy individuals, investigators found that a missense mutation in the gene SLC39A8 of SNP rs13107325 was associated with larger volumes in the bilateral putamen (left hemisphere t₁₇₀₅=8.66, p=5.35 x 10^-18, variance explained = 4.21%; right hemisphere t₁₇₀₅=8.90, p=6.80 x 10^-19, variance explained = 4.44%). The SNP rs13107325 has previously been found to be associated with schizophrenia, and as such, the investigators were able to replicate the positive association of SNP rs13107325 in the left putamen with data from 971 healthy adolescents (t₉₆₄=3.70, p=1.16 x 10^-4). The results of this study did not demonstrate an association with the right putamen (p=0.08).  Carriers of the risk allele SNP rs13107325 had lower expression of SLC39A8 in the putamen (t­₁₂₇= -3.87, 95% CI -6.51 to -1.73, p=0.0002). In the clinical sample of patients with schizophrenia and unaffected siblings, the rs13107325-putamen association was significantly weakened. Taken together, results from this study show a rs13107325-putamen association in adolescent brains that is weakened in schizophrenia; disruption of the association may be due to other genetic factors for schizophrenia. As SLC39A8 encodes a solute carrier transporterZIP8, the results from this study provide a new pathway for studying schizophrenia.

Click to read the study in JAMA Psychiatry

Image: PD

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