Within-family influences on dimensional neurobehavioral traits in a high-risk genetic model. Issue 14 (14th October 2022)

• Record Type: Journal Article
• Authors: Fiksinski, Ania M.; Heung, Tracy; Corral, Maria; Breetvelt, Elemi J.; Costain, Gregory; Marshall, Christian R.; Kahn, Rene S.; Vorstman, Jacob A.S.; Bassett, Anne S.
• Is Part Of: Psychological medicine. Volume 52:Issue 14(2022)
• Page Start: 3184
• Page End: 3192
• Publication Date: 2022-10-14
• Subjects: 22q11.2 deletion syndrome -- genetics -- quantitative traits -- schizophrenia -- shared variance -- variable expression; Psychiatry -- Periodicals; Medicine and psychology -- Periodicals; Clinical psychology -- Periodicals; 616.89
• DOI: 10.1017/S0033291720005279
• Languages: English
• ISSNs: 0033-2917

Abstract

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.