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 this paper we will review recent neuroimaging research in schizophrenia, with an aim to critically evaluate several recent proposals concerning the nature and the timing of the neuroanatomic abnormalities underlying the disorder. Specifically, enlargement of cerebrospinal fluid spaces, deficits in cortical gray matter, and reduced volume of mesiotemporal structures have all been reported in patients in the first episode of schizophrenia, their first-degree relatives, and individuals with schizotypal personality disorder, supporting the possibility that these abnormalities reflect a genetically mediated neurodevelopmental disorder. These findings from the empirical literature will be synthesized from the perspective of dual cytoarchitectonic trends theory of neurodevelopment, as well as in relation to current conceptions of the schizophrenia prodrome. We believe that the evidence shows that sufficient groundwork has been laid to begin longitudinal neuroimaging studies of adolescents at clinical risk for schizophrenia, in order to more definitively determine the pathophysiology of the disorder. Such information could have significant implications in terms of understanding the prediction, treatment, and ultimately the prevention of schizophrenia.

The purpose of the current study was to examine the predictive roles of stereotype threat and perceived discrimination and the mediating role of examiner-examinee racial discordance on neuropsychological performance in a non-clinical sample of African American and Caucasian individuals. Ninety-two African American (n = 45) and Caucasian (n = 47) adults were randomly assigned to either a stereotype threat or non-threat condition. Within each condition, participants were randomly assigned to either a same race or different race examiner. All participants underwent neuropsychological testing and completed a measure of perceived discrimination. African Americans in the stereotype threat condition performed significantly worse on global NP (Mz = −.30, 95% confidence interval [CI] [−0.07, −0.67] than African Americans in the non-threat condition (Mz = 0.09, CI [0.15, 0.33]. African Americans who reported high levels of perceived discrimination performed significantly worse on memory tests when tested by an examiner of a different race, Mz = −1.19, 95% CI [−1.78, −.54], than African Americans who were tested by an examiner of the same race, Mz = 0.24, 95% CI [−0.24, 0.72]. The current study underscores the importance of considering the role of contextual variables in neuropsychological performance, as these variables may obscure the validity of results among certain racial/ethnic groups. (JINS, 2013, 19, 1–10)

Neuropsychology is poised for transformations of its concepts and methods, leveraging advances in neuroimaging, the human genome project, psychometric theory, and information technologies. It is argued that a paradigm shift toward evidence-based science and practice can be enabled by innovations, including (1) formal definition of neuropsychological concepts and tasks in cognitive ontologies; (2) creation of collaborative neuropsychological knowledgebases; and (3) design of Web-based assessment methods that permit free development, large-sample implementation, and dynamic refinement of neuropsychological tests and the constructs these aim to assess. This article considers these opportunities, highlights selected obstacles, and offers suggestions for stepwise progress toward these goals. (JINS, 2011, 17, 000–000)

Animal word list generation (ANWLG) was administered to 47 first-episode schizophrenia (FES) participants and 31 controls. Fifty-nine left temporal lobe epilepsy (LTLE) participants were included as a comparison group with known temporal lobe damage and expected semantic deficits. Semantic knowledge was assessed with the Association Index (AI), a measure of the semantic relatedness of all consecutive ANWLG responses. Neuropsychological tests of language and executive functioning were also administered. Results showed that both FES and LTLE groups generated fewer ANWLG responses than controls, but only the LTLE participants obtained a lower AI relative to controls. FES participants did not differ from controls on the AI. FES and LTLE groups produced fewer semantic subcategories (clusters), however, only the LTLE group produced fewer words per subcategory compared to controls (cluster size). FES participants produced a higher rate of perseverative responses compared to the other groups. Finally, correlation analyses showed that for FES participants both executive and language tests significantly correlated with ANWLG total responses, while the correlation between ANWLG and only 1 language test was significant for LTLE participants. Taken together, the results suggest that reduced ANWLG output in FES participants may be best conceptualized as a deficit in the executive component of word list generation (i.e., semantic search/access, response monitoring) or global cognitive impairment. (JINS, 2003, 9, 384–393.)