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Fiksinski AM, Heung T, Corral M, et al. Within-family influences on dimensional neurobehavioral traits in a high-risk genetic model. Psychol Med. 2021;1-9doi: 10.1017/S0033291720005279.
Fiksinski, A. M., Heung, T., Corral, M., Breetvelt, E. J., Costain, G., Marshall, C. R., Kahn, R. S., Vorstman, J. A. S., & Bassett, A. S. (2021). Within-family influences on dimensional neurobehavioral traits in a high-risk genetic model. Psychological medicine, 1-9. https://doi.org/10.1017/S0033291720005279
Fiksinski, Ania M, et al. "Within-family influences on dimensional neurobehavioral traits in a high-risk genetic model." Psychological medicine vol. (2021): 1-9. doi: https://doi.org/10.1017/S0033291720005279
Fiksinski AM, Heung T, Corral M, Breetvelt EJ, Costain G, Marshall CR, Kahn RS, Vorstman JAS, Bassett AS. Within-family influences on dimensional neurobehavioral traits in a high-risk genetic model. Psychol Med. 2021 Jan 14;1-9. doi: 10.1017/S0033291720005279. Epub 2021 Jan 14. PMID: 33443009.
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Psychol Med. 2021 Jan 14;1-9. doi: 10.1017/S0033291720005279. Epub 2021 Jan 14.

Within-family influences on dimensional neurobehavioral traits in a high-risk genetic model.

Psychological medicine

Ania M Fiksinski, Tracy Heung, Maria Corral, Elemi J Breetvelt, Gregory Costain, Christian R Marshall, Rene S Kahn, Jacob A S Vorstman, Anne S Bassett

Affiliations

  1. Department of Psychiatry, Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands.
  2. Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
  3. The Dalglish Family 22q Clinic for 22q11.2 Deletion Syndrome, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
  4. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
  5. Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada.
  6. Program in Genetics and Genome Biology, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
  7. Genome Diagnostics, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
  8. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
  9. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  10. Toronto General Hospital Research Institute and Campbell Family Mental Health Research Institute, Toronto, Ontario, Canada.

PMID: 33443009 DOI: 10.1017/S0033291720005279

Abstract

BACKGROUND: Genotype-first and within-family studies can elucidate factors that contribute to psychiatric illness. Combining these approaches, we investigated the patterns of influence of parental scores, a high-impact variant, and schizophrenia on dimensional neurobehavioral phenotypes implicated in major psychiatric disorders.

METHODS: We quantitatively assessed cognitive (FSIQ, VIQ, PIQ), social, and motor functioning in 82 adult individuals with a de novo 22q11.2 deletion (22 with schizophrenia), and 148 of their unaffected parents. We calculated within-family correlations and effect sizes of the 22q11.2 deletion and schizophrenia, and used linear regressions to assess contributions to neurobehavioral measures.

RESULTS: Proband-parent intra-class correlations (ICC) were significant for cognitive measures (e.g. FSIQ ICC = 0.549, p < 0.0001), but not for social or motor measures. Compared to biparental scores, the 22q11.2 deletion conferred significant impairments for all phenotypes assessed (effect sizes -1.39 to -2.07 s.d.), strongest for PIQ. There were further decrements in those with schizophrenia. Regression models explained up to 37.7% of the variance in IQ and indicated that for proband IQ, parental IQ had larger effects than schizophrenia.

CONCLUSIONS: This study, for the first time, disentangles the impact of a high-impact variant from the modifying effects of parental scores and schizophrenia on relevant neurobehavioral phenotypes. The robust proband-parent correlations for cognitive measures, independent of the impact of the 22q11.2 deletion and of schizophrenia, suggest that, for certain phenotypes, shared genetic variation plays a significant role in expression. Molecular genetic and predictor studies are needed to elucidate shared factors and their contribution to psychiatric illness in this and other high-risk groups.

Keywords: 22q11.2 deletion syndrome; genetics; quantitative traits; schizophrenia; shared variance; variable expression

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