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Whole genome sequencing study of identical twins discordant for psychosis
Neuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.
Neuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.
Department of Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Departments of Psychology and Psychiatry, Yale University School of Medicine, CT, New Haven, United States.
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2024 (English)In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 14, no 1, article id 313Article in journal (Refereed) Published
Abstract [en]

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 FOXN1 and FLOT2 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.

Place, publisher, year, edition, pages
Springer Nature, 2024. Vol. 14, no 1, article id 313
National Category
Psychiatry Medical Genetics and Genomics Neurosciences
Identifiers
URN: urn:nbn:se:umu:diva-228276DOI: 10.1038/s41398-024-02982-0ISI: 001280904500001PubMedID: 39080272Scopus ID: 2-s2.0-85200037055OAI: oai:DiVA.org:umu-228276DiVA, id: diva2:1888062
Funder
NIH (National Institutes of Health), 5U01MH 109499-04NIH (National Institutes of Health), R01 MH052857Swedish Research Council, D0886501Region Stockholm, 20100305Region Stockholm, 20090183Available from: 2024-08-12 Created: 2024-08-12 Last updated: 2025-02-10Bibliographically approved

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Johansson, Viktoria

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