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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Davies, RW; Fiksinski, AM; Breetvelt, EJ; Williams, NM; Hooper, SR; Monfeuga, T; Bassett, AS; Owen, MJ; Gur, RE; Morrow, BE; McDonald-McGinn, DM; Swillen, A; Chow, EWC; van den Bree, M; Emanuel, BS; Vermeesch, JR; van Amelsvoort, T; Arango, C; Armando, M; Campbell, LE; Cubells, JF; Eliez, S; Garcia-Minaur, S; Gothelf, D; Kates, WR; Murphy, KC; Murphy, CM; Murphy, DG; Philip, N; Repetto, GM; Shashi, V; Simon, TJ; Suñer, DH; Vicari, S; Scherer, SW; International 22q11.2 Brain and Behavior Consortium, ; Bearden, CE; Vorstman, JAS

Published Date

  • December 2020

Published In

Volume / Issue

  • 26 / 12

Start / End Page

  • 1912 - 1918

PubMed ID

  • 33169016

Pubmed Central ID

  • PMC7975627

Electronic International Standard Serial Number (EISSN)

  • 1546-170X

Digital Object Identifier (DOI)

  • 10.1038/s41591-020-1103-1


  • eng

Conference Location

  • United States