Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.

In line with a dimensional approach to psychopathology, we examined whether psychosocial function and its relationship to neurocognition and clinical symptoms differ across schizophrenia and bipolar disorder subgroups with and without a history of affective or psychotic episodes. From the TOP study, a heterogeneous sample of individuals with schizophrenia spectrum disorders without (n = 60) and with a history of affective episodes (n = 54); individuals with bipolar spectrum disorders with (n = 64) and without a history of psychosis (n = 56) and healthy controls (n = 268) participated. Psychosocial functioning was measured with the Social Functioning Scale (self-rated) and the Global Assessment of Functioning Scale (clinician-rated), neurocognition with a comprehensive neuropsychological test battery, and symptoms with Inventory of Depressive Symptomatology, Young Mania Rating Scale, and Positive and Negative Syndrome Scale. Clinician-rated functioning was poorer in schizophrenia groups than in bipolar groups, but self-rated functioning was similar across all clinical groups and poorer than in controls. Neurocognition and current clinical symptoms were associated with psychosocial function in bivariate analyses, but current symptoms had a greater independent contribution to functioning than neurocognition across clinical groups in multivariate analyses. Despite differences in neurocognition and psychosocial function, groups showed the same pattern in prediction of functioning irrespective of DSM-IV or clinical definition. (JINS, 2010, 16, 771–783.)

Social cognition and learning potential have been proposed as mediating variables between neurocognition and functional outcome in schizophrenia. The present study examined this relation in a schizophrenia group (N = 26) with normal IQ. Neurocognition was measured with a composite score from tests of verbal learning, psychomotor speed, and executive functioning. Functional outcome was defined as social problem-solving skills and assessed with a role-play test. Social cognition was indexed by tests of visual and auditory emotion perception; and learning potential by estimating a gain score using a triple administration of the WCST. Neurocognition was confirmed to be a strong predictor of social problem-solving, and emotion perception was related to both neurocognition and social problem-solving. When controlling for emotion perception, the association between neurocognition and social problem-solving was weakened, implying a mediating role of emotion perception. Learning potential was not significantly related to neurocognition or social problem-solving, and thus not found to mediate the studied relation. In conclusion, our study indicates that emotion perception is a mediator between neurocognition and functional outcome as assessed with a social problem-solving task and thus a key factor in understanding functional outcome of schizophrenia. (JINS, 2008, 14, 279–288.)

The purpose of the study was to examine the hypothesis that distractibility is a fundamental characteristic of mild closed head injury (MHI). The claim that cognitive symptoms in MHI are due to a mild type of frontotemporal injury was also investigated. Cognitive event-related potentials (ERPs), accuracy and reaction time to target stimuli in a dichotic listening paradigm, and neuropsychological test results were studied in patients with MHI (N = 15), patients with verified frontal lobe damage (N = 10), and healthy controls (N = 13). Information processing reflecting target detection (N2, P3b) and sustained selective attention (processing negativity) was studied. The MHI and frontal patients did not differ on behavioral measures, except that the MHI group had significantly longer reaction times to target stimuli in the ERP task. Both patient groups had deviant ERPs compared with controls, but their ERP patterns differed in important respects. Contrary to expectations, the MHI patients had the most abnormal ERPs. They showed significantly smaller N2 and Nd amplitudes than frontal patients and controls, indicating that the mediating cognitive mechanisms were not equivalent in MHI and frontal injury. The data suggest that MHI patients allocated less processing resources to the task than either the control subjects or the patients with frontal lobe damage.