Type

Journal Article

Authors

Stanley Zammit
James T Walters
Michael J Owen
Michael C O'Donovan
George Davey Smith
Peter B Jones
David E J Linden
Glyn Lewis
Peter Holmans
Mary Cannon
and 5 others

Subjects

Psychiatry

Topics
parents and children single nucleotide polymorphisms well being depressive disorder genome wide association study odds ratio quality control longitudinal study

Phenotypic Manifestation of Genetic Risk for Schizophrenia During Adolescence in the General Population. (2016)

Abstract Schizophrenia is a highly heritable, polygenic condition characterized by a relatively diverse phenotype and frequent comorbid conditions, such as anxiety and depression. At present, limited evidence explains how genetic risk for schizophrenia is manifest in the general population. To investigate the extent to which genetic risk for schizophrenia is associated with different phenotypes during adolescence in a population-based birth cohort. This cohort study used data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Of 14 062 children in the birth cohort, genetic data were available for 9912 adolescents. Data were collected periodically from September 6, 1990, and collection is ongoing. Data were analyzed from March 4 to August 13, 2015. Polygenic risk scores (PRSs) for schizophrenia generated for individuals in the ALSPAC cohort using results of the second Psychiatric Genomics Consortium Schizophrenia genome-wide association study as a training set. Logistic regression was used to assess associations between the schizophrenia PRS and (1) psychotic experiences (Psychosis-Like Symptom Interview at 12 and 18 years of age), (2) negative symptoms (Community Assessment of Psychic Experiences at 16.5 years of age), (3) depressive disorder (Development and Well-Being Assessment at 15.5 years of age), and (4) anxiety disorder (Development and Well-Being Assessment at 15.5 years of age) in adolescence. Of the 8230 ALSPAC participants whose genetic data passed quality control checks (51.2% male, 48.8% female), 3676 to 5444 participated in assessments from 12 to 18 years of age. The PRSs created using single-nucleotide polymorphisms with a training-set P ≤ .05 threshold were associated with negative symptoms (odds ratio [OR] per SD increase in PRS, 1.21; 95% CI, 1.08-1.36; R2 = 0.007) and anxiety disorder (OR per SD increase in PRS, 1.17; 95% CI, 1.06- 1.29; R2 = 0.005). No evidence was found of an association between schizophrenia PRS and psychotic experiences (OR per SD increase in PRS, 1.08; 95% CI, 0.98-1.19; R2 = 0.001) or depressive disorder (OR per SD increase in PRS, 1.02; 95% CI, 0.91-1.13; R2 = 0.00005). Results were mostly consistent across different training-set P value thresholds and using different cutoffs and measures of the psychopathological outcomes. This study demonstrates polygenic overlaps between common genetic polymorphisms associated with schizophrenia and negative symptoms and anxiety disorder but not with psychotic experiences or depression. Because the genetic risk for schizophrenia appears to be manifest as anxiety and negative symptoms during adolescence, a greater focus on these phenotypes rather than on psychotic experiences might be required for prediction of transition in at-risk samples.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Stanley Zammit, James T Walters, Michael J Owen, Michael C O'Donovan, George Davey Smith, Peter B Jones, David E J Linden, Glyn Lewis, Peter Holmans, Mary Cannon and 5 others

Experts in our system

1
Stanley Zammit
Royal College of Surgeons in Ireland
Total Publications: 6
 
2
James Walters
Trinity College Dublin
Total Publications: 12
 
3
Michael J. Owen
Trinity College Dublin
Total Publications: 24
 
4
Michael C O'Donovan
Trinity College Dublin
Total Publications: 23
 
5
P B Jones
Trinity College Dublin
Total Publications: 14
 
6
Glyn Lewis
Royal College of Surgeons in Ireland
Total Publications: 8
 
7
Peter Holmans
Trinity College Dublin
Total Publications: 9
 
8
Mary Cannon
Royal College of Surgeons in Ireland
Total Publications: 90