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Multi-Trait Analysis of GWAS and Biological Insights Into Cognition: A Response to Hill (2018).

  • Author(s): Lam, Max;
  • Trampush, Joey W;
  • Yu, Jin;
  • Knowles, Emma;
  • Djurovic, Srdjan;
  • Melle, Ingrid;
  • Sundet, Kjetil;
  • Christoforou, Andrea;
  • Reinvang, Ivar;
  • DeRosse, Pamela;
  • Lundervold, Astri J;
  • Steen, Vidar M;
  • Espeseth, Thomas;
  • Räikkönen, Katri;
  • Widen, Elisabeth;
  • Palotie, Aarno;
  • Eriksson, Johan G;
  • Giegling, Ina;
  • Konte, Bettina;
  • Roussos, Panos;
  • Giakoumaki, Stella;
  • Burdick, Katherine E;
  • Payton, Antony;
  • Ollier, William;
  • Chiba-Falek, Ornit;
  • Attix, Deborah K;
  • Need, Anna C;
  • Cirulli, Elizabeth T;
  • Voineskos, Aristotle N;
  • Stefanis, Nikos C;
  • Avramopoulos, Dimitrios;
  • Hatzimanolis, Alex;
  • Arking, Dan E;
  • Smyrnis, Nikolaos;
  • Bilder, Robert M;
  • Freimer, Nelson A;
  • Cannon, Tyrone D;
  • London, Edythe;
  • Poldrack, Russell A;
  • Sabb, Fred W;
  • Congdon, Eliza;
  • Conley, Emily Drabant;
  • Scult, Matthew A;
  • Dickinson, Dwight;
  • Straub, Richard E;
  • Donohoe, Gary;
  • Morris, Derek;
  • Corvin, Aiden;
  • Gill, Michael;
  • Hariri, Ahmad R;
  • Weinberger, Daniel R;
  • Pendleton, Neil;
  • Bitsios, Panos;
  • Rujescu, Dan;
  • Lahti, Jari;
  • Hellard, Stephanie Le;
  • Keller, Matthew C;
  • Andreassen, Ole A;
  • Glahn, David C;
  • Malhotra, Anil K;
  • Lencz, Todd
  • et al.

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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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