MPC Member Publications

This database contains a listing of population studies publications written by MPC Members. Anyone can add a publication by an MPC student, faculty, or staff member to this database; new citations will be reviewed and approved by MPC administrators.

Full Citation

Title: Psychological Medicine Using multivariate endophenotypes to identify psychophysiological mechanisms associated with polygenic scores for substance use, schizophrenia, and education attainment

Citation Type: Journal Article

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DOI: 10.1017/S0033291721000763

Abstract: Original Article Cite this article: Harper J, Liu M, Malone SM, McGue M, Iacono WG, Vrieze SI (2021). Using multivariate endophenotypes to identify psychophysiological mechanisms associated with polygenic scores for substance use, schizophrenia, and education attainment. Psychological Medicine 1-11. https://doi. 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 geno-typed 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. schizo-phrenia PGS correlated positively with alcohol/nicotine/cannabis PGSs). Schizophrenia PGS was negatively associated with an event-related P3/δ component [β = −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 (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, schizophre-nia, and educational attainment PGSs and represent promising targets for future research.

Url: https://doi.org/10.1017/S0033291721000763

User Submitted?: No

Authors: Harper, Jeremy; Liu, Mengzhen; Malone, Stephen M.; Mcgue, Matthew; Iacono, William G; Vrieze, Scott

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