Multi-Trait Analysis of GWAS and Biological Insights Into Cognition: A Response to Hill (2018).
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'.
Lam, M; Trampush, JW; Yu, J; Knowles, E; Djurovic, S; Melle, I; Sundet, K; Christoforou, A; Reinvang, I; DeRosse, P; Lundervold, AJ; Steen, VM; Espeseth, T; Räikkönen, K; Widen, E; Palotie, A; Eriksson, JG; Giegling, I; Konte, B; Roussos, P; Giakoumaki, S; Burdick, KE; Payton, A; Ollier, W; Chiba-Falek, O; Attix, DK; Need, AC; Cirulli, ET; Voineskos, AN; Stefanis, NC; Avramopoulos, D; Hatzimanolis, A; Arking, DE; Smyrnis, N; Bilder, RM; Freimer, NA; Cannon, TD; London, E; Poldrack, RA; Sabb, FW; Congdon, E; Conley, ED; Scult, MA; Dickinson, D; Straub, RE; Donohoe, G; Morris, D; Corvin, A; Gill, M; Hariri, AR; Weinberger, DR; Pendleton, N; Bitsios, P; Rujescu, D; Lahti, J; Hellard, SL; Keller, MC; Andreassen, OA; Glahn, DC; Malhotra, AK; Lencz, T
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