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.

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.

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 [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).

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.

为了更好地描述基于大脑的精神病理学和心理特征的多基因责任机制，我们扩展了我们之前的报告（Liu 等人。心理生理内表型来描述已知精神分裂症基因位点的机制。心理医学，2017），仅关注精神分裂症，以测试多变量心理生理学候选内表型（包括θ / δ振荡活动的新测量值）与一系列多基因评分（PGS）之间的关联，即酒精/大麻/尼古丁使用，更新的精神分裂症 PGS（包含比 52 个更多的全基因组显着位点我们之前报告中使用的 PGS）和教育程度。

对基于社区的大型双胞胎/家庭样本 ( N = 4893) 进行了全基因组基因分型和估算。PGS 是为酒精使用、定期开始吸烟、终生使用大麻、精神分裂症和教育程度而构建的。评估了 11 种内表型：视觉古怪任务事件相关脑电图 (EEG) 测量（目标相关顶叶 P3 振幅、额叶θ和顶叶δ能量/试验间期聚类）、带限静息态脑电图功率、反眼跳误差速度。主成分分析利用内表型之间的协变来提取较少数量的有意义的维度/成分用于统计分析。

内表型是可遗传的。PGS 显示出预期的相互关联（例如，精神分裂症 PGS 与酒精/尼古丁/大麻 PGS 呈正相关）。精神分裂症 PGS 与事件相关的 P3/ δ分量呈负相关 [ β = −0.032，非参数 bootstrap 95% 置信区间 (CI) −0.059 至 −0.003]。前额叶控制成分（与事件相关的θ / 反眼跳错误）与酒精呈负相关（β = -0.034，95% CI -0.063 至 -0.006）和经常吸烟的 PGS（β = -0.032，95% CI -0.061 至 - 0.005) 并与受教育程度 PGS 呈正相关 ( β = 0.031, 95% CI 0.003–0.058)。

证据表明，决策的多变量内表型 (P3/ δ ) 和认知/注意力控制 ( θ /antisaccade error) 与酒精/尼古丁、精神分裂症和受教育程度 PGS 相关，代表了未来研究的有希望的目标。