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

  • Max Lam (a1), Joey W. Trampush (a2), Jin Yu (a3), Emma Knowles (a4), Srdjan Djurovic (a5) (a6), Ingrid Melle (a6) (a7), Kjetil Sundet (a7) (a8), Andrea Christoforou (a9), Ivar Reinvang (a8), Pamela DeRosse (a3), Astri J. Lundervold (a10), Vidar M. Steen (a6) (a9), Thomas Espeseth (a7) (a8), Katri Räikkönen (a11), Elisabeth Widen (a12), Aarno Palotie (a12) (a13) (a14), Johan G. Eriksson (a15) (a16) (a17), Ina Giegling (a18), Bettina Konte (a18), Panos Roussos (a19) (a20) (a21), Stella Giakoumaki (a22), Katherine E. Burdick (a18) (a21) (a23), Antony Payton (a24), William Ollier (a24) (a25), Ornit Chiba-Falek (a26), Deborah K. Attix (a26) (a27), Anna C. Need (a28), Elizabeth T. Cirulli (a29), Aristotle N. Voineskos (a30), Nikos C. Stefanis (a31) (a32) (a33), Dimitrios Avramopoulos (a34) (a35), Alex Hatzimanolis (a31) (a32) (a33), Dan E. Arking (a35), Nikolaos Smyrnis (a31) (a32), Robert M. Bilder (a36), Nelson A. Freimer (a36), Tyrone D. Cannon (a37), Edythe London (a36), Russell A. Poldrack (a38), Fred W. Sabb (a39), Eliza Congdon (a36), Emily Drabant Conley (a40), Matthew A. Scult (a41), Dwight Dickinson (a42), Richard E. Straub (a43), Gary Donohoe (a44), Derek Morris (a44), Aiden Corvin (a45), Michael Gill (a45), Ahmad R. Hariri (a41), Daniel R. Weinberger (a43), Neil Pendleton (a46), Panos Bitsios (a47), Dan Rujescu (a18), Jari Lahti (a11) (a48), Stephanie Le Hellard (a6) (a9), Matthew C. Keller (a49), Ole A. Andreassen (a6) (a7) (a50), David C. Glahn (a4), Anil K. Malhotra (a3) (a51) (a52) and Todd Lencz (a3) (a51) (a52)...


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’.


Corresponding author

address for correspondence: Todd Lencz, Zucker Hillside Hospital, Division of Psychiatry Research, 75-59 263rd Street, Glen Oaks, NY 11004, USA. E-mail:


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Hill, W. D. (2018). Comment on ‘large-scale cognitive GWAS meta-analysis reveals tissue-specific neural expression and potential nootropic drug targets’ by Lam et al. Twin Research and Human Genetics, 21, 8488.
Lam, M., Trampush, J. W., Yu, J., Knowles, E., Davies, G., Liewald, D. C., . . . Lencz, T. (2017). Large-scale cognitive GWAS meta-Analysis reveals tissue-specific neural expression and potential nootropic drug targets. Cell Reports, 21, 25972613.
Okbay, A., Beauchamp, J. P., Fontana, M. A., Lee, J. J., Pers, T. H., Rietveld, C. A., . . . Benjamin, D. J. (2016). Genome-wide association study identifies 74 loci associated with educational attainment. Nature, 533, 539542.
Turley, P., Walters, R. K., Maghzian, O., Okbay, A., Lee, J. J., Fontana, M. A., . . . Social Science Genetic Association Consortium. (2018). Multi-trait analysis of genome-wide association summary statistics using MTAG. Nature Genetics, 50, 229237.
Walters, R. T. (2016, April 25). Response to query on LD score regression user forum. Retrieved February 1, 2018, from!topic/ldsc_users/UY2vlI4AJbc
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Twin Research and Human Genetics
  • ISSN: 1832-4274
  • EISSN: 1839-2628
  • URL: /core/journals/twin-research-and-human-genetics
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