Using multivariate endophenotypes to identify psychophysiological mechanisms associated with polygenic scores for substance use, schizophrenia, and education attainment.
Psychol Med
; : 1-11, 2021 Mar 18.
Article
en En
| MEDLINE
| ID: mdl-33731234
ABSTRACT
BACKGROUND:
To better characterize brain-based mechanisms of polygenic liability for psychopathology and psychological traits, we extended our previous report (Liu et al. Psychophysiological endophenotypes to characterize mechanisms of known schizophrenia genetic loci. Psychological Medicine, 2017), focused solely on schizophrenia, to test the association between multivariate psychophysiological candidate endophenotypes (including novel measures of θ/δ oscillatory activity) and a range of polygenic scores (PGSs), namely alcohol/cannabis/nicotine use, an updated schizophrenia PGS (containing 52 more genome-wide significant loci than the PGS used in our previous report) and educational attainment.METHOD:
A large community-based twin/family sample (N = 4893) was genome-wide genotyped and imputed. PGSs were constructed for alcohol use, regular smoking initiation, lifetime cannabis use, schizophrenia, and educational attainment. Eleven endophenotypes were assessed visual oddball task event-related electroencephalogram (EEG) measures (target-related parietal P3 amplitude, frontal θ, and parietal δ energy/inter-trial phase clustering), band-limited resting-state EEG power, antisaccade error rate. Principal component analysis exploited covariation among endophenotypes to extract a smaller number of meaningful dimensions/components for statistical analysis.RESULTS:
Endophenotypes were heritable. PGSs showed expected intercorrelations (e.g. schizophrenia PGS correlated positively with alcohol/nicotine/cannabis PGSs). Schizophrenia PGS was negatively associated with an event-related P3/δ component [ß = -0.032, nonparametric bootstrap 95% confidence interval (CI) -0.059 to -0.003]. A prefrontal control component (event-related θ/antisaccade errors) was negatively associated with alcohol (ß = -0.034, 95% CI -0.063 to -0.006) and regular smoking PGSs (ß = -0.032, 95% CI -0.061 to -0.005) and positively associated with educational attainment PGS (ß = 0.031, 95% CI 0.003-0.058).CONCLUSIONS:
Evidence suggests that multivariate endophenotypes of decision-making (P3/δ) and cognitive/attentional control (θ/antisaccade error) relate to alcohol/nicotine, schizophrenia, and educational attainment PGSs and represent promising targets for future research.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Psychol Med
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos