4.7 Article

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

期刊

PSYCHOLOGICAL MEDICINE
卷 52, 期 14, 页码 3184-3192

出版社

CAMBRIDGE UNIV PRESS
DOI: 10.1017/S0033291720005279

关键词

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

资金

  1. Canadian Institutes of Health Research [PJT-148924, MOP-313331, MOP-111238, MOP-38099]
  2. Ter Meulen Grant of the Royal Netherlands Academy of Arts and Sciences
  3. UMCU Strategic Network Development Grant
  4. Mr. Rajeeb Mukherjee BSc (Hons) (London School of Economics) Fellowship in Schizophrenia
  5. McLaughlin Centre Accelerator grants
  6. SickKids Psychiatry Associates Chair in Developmental Psychopathology
  7. University of Toronto
  8. University Health Network

向作者/读者索取更多资源

This study investigated the impact of parental scores, a high-impact variant, and schizophrenia on neurobehavioral phenotypes in psychiatric disorders. The findings revealed significant impairments in cognitive measures due to the 22q11.2 deletion compared to parental scores, with the strongest effects on PIQ. Additionally, there were further decrements in those with schizophrenia, suggesting shared genetic variation plays a significant role in certain phenotypes.
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.

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