Key result
Schizophrenia polygenic scores were negatively associated with an event-related P3/δ component, while a prefrontal control component was associated with alcohol, smoking, and educational attainment polygenic scores.
Why the study?
To better characterize brain-based mechanisms of polygenic liability for psychopathology and psychological traits by testing associations between multivariate psychophysiological candidate endophenotypes and various polygenic scores.
Cross-Sectional (n=4,893)
Multivariate endophenotypes of decision-making and cognitive/attentional control relate to polygenic scores for alcohol/nicotine use, schizophrenia, and educational attainment, representing potential biobehavioral mechanisms of polygenic liability.
Answers are grounded in this paper and cite their sources.
Novel endophenotypes extend schizophrenia findings to broader psychopathology; hypothesis-generating and requires validation before clinical translation.
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 ofθ/δoscillatory 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, frontalθ, and parietalδenergy/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/δcomponent [β= −0.032, nonparametric bootstrap 95% confidence interval (CI) −0.059 to −0.003]. A prefrontal control component (event-relatedθ/antisaccade errors) was negatively associated with alcohol (β= −0.034, 95% CI −0.063 to −0.006) and regular smoking PGSs (β= −0.032, 95% CI −0.061 to −0.005) and positively associated with educational attainment PGS (β= 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.
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Harper et al. (2021) conducted a cross-sectional in Polygenic liability for psychopathology and psychological traits (n=4,893). Polygenic scores for substance use, schizophrenia, and educational attainment was evaluated on Association between schizophrenia polygenic score and event-related P3/δ component (PC3) (β = -0.032, 95% CI -0.059 to -0.003). Schizophrenia polygenic scores were negatively associated with an event-related P3/δ component, while a prefrontal control component was associated with alcohol, smoking, and educational attainment polygenic scores.
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