Using common genetic variation to examine phenotypic expression and risk prediction in 22q11.2 deletion syndrome

International 22q11.2 Brain and Behavior Consortium, Rosemarie Fritsch

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

72 Citas (Scopus)


The 22q11.2 deletion syndrome (22q11DS) is associated with a 20–25% risk of schizophrenia. In a cohort of 962 individuals with 22q11DS, we examined the shared genetic basis between schizophrenia and schizophrenia-related early trajectory phenotypes: sub-threshold symptoms of psychosis, low baseline intellectual functioning and cognitive decline. We studied the association of these phenotypes with two polygenic scores, derived for schizophrenia and intelligence, and evaluated their use for individual risk prediction in 22q11DS. Polygenic scores were not only associated with schizophrenia and baseline intelligence quotient (IQ), respectively, but schizophrenia polygenic score was also significantly associated with cognitive (verbal IQ) decline and nominally associated with sub-threshold psychosis. Furthermore, in comparing the tail-end deciles of the schizophrenia and IQ polygenic score distributions, 33% versus 9% of individuals with 22q11DS had schizophrenia, and 63% versus 24% of individuals had intellectual disability. Collectively, these data show a shared genetic basis for schizophrenia and schizophrenia-related phenotypes and also highlight the future potential of polygenic scores for risk stratification among individuals with highly, but incompletely, penetrant genetic variants.

Idioma originalInglés
Páginas (desde-hasta)1912-1918
Número de páginas7
PublicaciónNature Medicine
EstadoPublicada - dic. 2020

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© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.


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