Multi-Trait analysis of gwas and biological insights into cognition: A response to hill (2018)

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Abstract

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'.

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Lam, M., Trampush, J. W., Yu, J., Knowles, E., Djurovic, S., Melle, I., … Lencz, T. (2018). Multi-Trait analysis of gwas and biological insights into cognition: A response to hill (2018). Twin Research and Human Genetics, 21(5), 394–397. https://doi.org/10.1017/thg.2018.46

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