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

Stefano Vicari, Mariasofia Houben, Robert W. Davies, Ania M. Fiksinski, Elemi J. Breetvelt, Nigel M. Williams, Stephen R. Hooper, Thomas Monfeuga, Anne S. Bassett, Michael J. Owen, Raquel E. Gur, Bernice E. Morrow, Donna M. Mcdonald-Mcginn, Ann Swillen, Eva W. C. Chow, Marianne Van Den Bree, Beverly S. Emanuel, Joris R. Vermeesch, Therese Van Amelsvoort, Celso ArangoMarco Armando, Linda E. Campbell, Joseph F. Cubells, Stephan Eliez, Sixto Garcia-Minaur, Doron Gothelf, Wendy R. Kates, Kieran C. Murphy, Clodagh M. Murphy, Declan G. Murphy, Nicole Philip, Gabriela M. Repetto, Vandana Shashi, Tony J. Simon, Damiàn Heine Suñer, Stephen W. Scherer, Michael P. Epstein, Stephen T. Warren, Sinead Morrison, Samuel Chawner, Claudia Vingerhoets, Jeroen Breckpot, Elfi Vergaelen, Annick Vogels, Stephen Monks, Sarah E. Prasad, Corrado Sandini, Maude Schneider, Johanna Maeder, David Fraguas, Rens Evers, Flora Tassone, Jaume Morey-Canyelles, Opal Y. Ousley, Kevin M. Antshel, Wanda Fremont, Rosemarie Fritsch, Claudia Ornstein, Eileen M. Daly, Gregory A. Costain, Erik Boot, Tracy Heung, T. Blaine Crowley, Elaine H. Zackai, Monica E. Calkins, Ruben C. Gur, Kathryn L. Mccabe, Tiffany Busa, Kelly Schoch, Sasja N. Duijff, René S. Kahn, Michiel Houben, Leila Kushan, Maria Jalbrzikowski, Miri Carmel, Ehud Mekori-Domachevsky, Elena Michaelovsky, Ronnie Weinberger, Carrie E. Bearden, Jacob A. S. Vorstman

Research output: Contribution to journalArticle

15 Citations (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.
Original languageEnglish
Pages (from-to)1912-1918
Number of pages7
JournalNature Medicine
Publication statusPublished - 2020


  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Cognitive Dysfunction
  • Cohort Studies
  • DiGeorge Syndrome
  • Female
  • Genetic Variation
  • Humans
  • Intellectual Disability
  • Male
  • Middle Aged
  • Multifactorial Inheritance
  • Phenotype
  • Risk Factors
  • Schizophrenia
  • Young Adult


Dive into the research topics of 'Using common genetic variation to examine phenotypic expression and risk prediction in 22q11.2 deletion syndrome'. Together they form a unique fingerprint.

Cite this