A normative chart for cognitive development in a genetically selected population

Ania M Fiksinski*, Carrie E Bearden, 22q11DS International Consortium on Brain and Behavior, Anne S Bassett, René S Kahn, Janneke R Zinkstok, Stephen R Hooper, Wanda Tempelaar, Donna McDonald-McGinn, Ann Swillen, Beverly Emanuel, Bernice Morrow, Raquel Gur, Eva Chow, Marianne van den Bree, Joris Vermeesch, Stephen Warren, Michael Owen, Therese van Amelsvoort, Stephan EliezDoron Gothelf, Celso Arango, Wendy Kates, Tony Simon, Kieran Murphy, Gabriela Repetto, Damian Heine Suner, Stefano Vicari, Joseph Cubells, Marco Armando, Nicole Philip, Linda Campbell, Sixto Garcia-Minaur, Maude Schneider, Vandana Shashi, Jacob Vorstman, Elemi J Breetvelt

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1379-1386
Number of pages8
Issue number7
Publication statusPublished - Jun 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to American College of Neuropsychopharmacology.


Dive into the research topics of 'A normative chart for cognitive development in a genetically selected population'. Together they form a unique fingerprint.

Cite this