Identical twins with psychosis carry different genetic mutations
Researchers sequenced 17 pairs of identical twins where one developed schizophrenia or bipolar disorder and the other didn't—finding rare genetic variants unique to the affected twin. The discovery suggests that mutations occurring after conception, not just inherited DNA, may trigger psychosis, potentially reshaping how psychiatrists understand and diagnose these disorders.
Originaltitel: Whole genome sequencing study of identical twins discordant for psychosis
<p>Monozygotic (MZ) twins are often thought to have identical genomes, but recent work has shown that early post-zygotic events can result in a spectrum of DNA variants that are different between MZ twins. Such variants may explain phenotypic discordance and contribute to disease etiology. Here we performed whole genome sequencing in 17 pairs of MZ twins discordant for a psychotic disorder (schizophrenia, schizoaffective disorder or bipolar disorder). We examined various classes of rare variants that are discordant within a twin pair. We identified four genes harboring rare, predicted deleterious missense variants that were private to an affected individual in the cohort. Variants in <em>FOXN1</em> and <em>FLOT2</em> would have been categorized as damaging from recent schizophrenia and bipolar exome sequencing studies. Additionally, we identified four rare genic copy number variants (CNVs) private to an affected sample, two of which overlapped genes that have shown evidence for association with schizophrenia or bipolar disorder. One such CNV was a 3q29 duplication previously implicated in autism and developmental delay. We have performed the largest MZ twin study for discordant psychotic phenotypes to date. These findings warrant further investigation using other analytical approaches.</p>