- Title
- A normative chart for cognitive development in a genetically selected population
- Creator
- Fiksinski, Ania M.; Bearden, Carrie E.; Morrow, Bernice; Gur, Raquel; Chow, Eva; van den Bree, Marianne; Vermeesch, Joris; Warren, Stephen; Owen, Michael; van Amelsvoort, Therese; Eliez, Stephan; Gothelf, Doron; Bassett, Anne S.; Arango, Celso; Kates, W; Simon, T; Murphy, K; Repetto, G; Suner, DH; Vicari, S; Cubells, J; Armando, M; Philip, N; Kahn, René S.; Campbell, Linda; Garcia-Minaur, S; Schneider, M; Shashi, V; 22q11DS International Consortium on Brain and Behavior; Vorstman, J; Breetvelt, EJ; Zinkstok, Janneke R.; Hooper, Stephen R.; Tempelaar, Wanda; McDonald-McGinn, Donna; Swillen, Ann; Emanuel, Beverly
- Relation
- Neuropsychopharmacology Vol. 47, Issue 7, p. 1379-1386
- Publisher Link
- http://dx.doi.org/10.1038/s41386-021-00988-6
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2022
- Description
- Certain pathogenic genetic variants impact neurodevelopment and cause deviations from typical cognitive trajectories. Understanding variant-specific cognitive trajectories is clinically important for informed monitoring and identifying patients at risk for comorbid conditions. Here, we demonstrate a variant-specific normative chart for cognitive development for individuals with 22q11.2 deletion syndrome (22q11DS). We used IQ data from 1365 individuals with 22q11DS to construct variant-specific normative charts for cognitive development (Full Scale, Verbal, and Performance IQ). This allowed us to calculate Z-scores for each IQ datapoint. Then, we calculated the change between first and last available IQ assessments (delta Z-IQ-scores) for each individual with longitudinal IQ data (n = 708). We subsequently investigated whether using the variant-specific IQ-Z-scores would decrease required sample size to detect an effect with schizophrenia risk, as compared to standard IQ-scores. The mean Z-IQ-scores for FSIQ, VIQ, and PIQ were close to 0, indicating that participants had IQ-scores as predicted by the normative chart. The mean delta-Z-IQ-scores were equally close to 0, demonstrating a good fit of the normative chart and indicating that, as a group, individuals with 22q11DS show a decline in IQ-scores as they grow into adulthood. Using variant-specific IQ-Z-scores resulted in 30% decrease of required sample size, as compared to the standard IQ-based approach, to detect the association between IQ-decline and schizophrenia (p < 0.01). Our findings suggest that using variant-specific normative IQ data significantly reduces required sample size in a research context, and may facilitate a more clinically informative interpretation of IQ data. This approach allows identification of individuals that deviate from their expected, variant-specific, trajectory. This group may be at increased risk for comorbid conditions, such as schizophrenia in the case of 22q11DS.
- Subject
- normative chart; cognitive development; pathogenic genetic variants; comorbid conditions
- Identifier
- http://hdl.handle.net/1959.13/1468103
- Identifier
- uon:47995
- Identifier
- ISSN:0893-133X
- Language
- eng
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