Using common genetic variation to examine phenotypic expression and risk prediction in 22q11.2 deletion syndrome.
Adolescent
Adult
Aged
Child
Child, Preschool
Cognitive Dysfunction
/ epidemiology
Cohort Studies
DiGeorge Syndrome
/ epidemiology
Female
Genetic Variation
/ genetics
Humans
Intellectual Disability
/ epidemiology
Male
Middle Aged
Multifactorial Inheritance
/ genetics
Phenotype
Risk Factors
Schizophrenia
/ epidemiology
Young Adult
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
06
11
2019
accepted:
14
09
2020
pubmed:
11
11
2020
medline:
29
1
2021
entrez:
10
11
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33169016
doi: 10.1038/s41591-020-1103-1
pii: 10.1038/s41591-020-1103-1
pmc: PMC7975627
mid: NIHMS1680050
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1912-1918Subventions
Organisme : NIMH NIH HHS
ID : U01 MH119758
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH101719
Pays : United States
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : U01 MH119740
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH101722
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH101720
Pays : United States
Organisme : MRF
ID : MRF_MRF-154-0001-RG-SKUSE
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : U01 MH119736
Pays : United States
Organisme : Medical Research Council
ID : MR/L011166/1
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : U01 MH119738
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH116473
Pays : United States
Organisme : Department of Health
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : R01 MH085953
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH064824
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH119741
Pays : United States
Organisme : Medical Research Council
ID : MR/N026063/1
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : U01 MH101724
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : K01 MH112774
Pays : United States
Organisme : Wellcome Trust
ID : 102428/Z/13/Z
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : U01 MH101723
Pays : United States
Investigateurs
Michael P Epstein
(MP)
Stephen T Warren
(ST)
Sinead Morrison
(S)
Samuel Chawner
(S)
Claudia Vingerhoets
(C)
Jeroen Breckpot
(J)
Elfi Vergaelen
(E)
Annick Vogels
(A)
Stephen Monks
(S)
Sarah E Prasad
(SE)
Corrado Sandini
(C)
Maude Schneider
(M)
Johanna Maeder
(J)
David Fraguas
(D)
Rens Evers
(R)
Flora Tassone
(F)
Jaume Morey-Canyelles
(J)
Opal Y Ousley
(OY)
Kevin M Antshel
(KM)
Wanda Fremont
(W)
Rosemarie Fritsch
(R)
Claudia Ornstein
(C)
Eileen M Daly
(EM)
Gregory A Costain
(GA)
Erik Boot
(E)
Tracy Heung
(T)
T Blaine Crowley
(TB)
Elaine H Zackai
(EH)
Monica E Calkins
(ME)
Ruben C Gur
(RC)
Kathryn L McCabe
(KL)
Tiffany Busa
(T)
Kelly Schoch
(K)
Maria Pontillo
(M)
Sasja N Duijff
(SN)
René S Kahn
(RS)
Michiel Houben
(M)
Leila Kushan
(L)
Maria Jalbrzikowski
(M)
Miri Carmel
(M)
Ehud Mekori-Domachevsky
(E)
Elena Michaelovsky
(E)
Ronnie Weinberger
(R)
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