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

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

Research output: Contribution to journalArticle

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'.

Original languageEnglish (US)
Pages (from-to)394-397
Number of pages4
JournalTwin Research and Human Genetics
Volume21
Issue number5
DOIs
StatePublished - Oct 1 2018

Keywords

  • Calcium channel
  • Cerebellum
  • Gene expression
  • General cognitive ability
  • Gwas
  • Neurodevelopment
  • Nootropics
  • Potassium channel
  • Synapse

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology
  • Genetics(clinical)

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  • Cite this

    Lam, M., Trampush, J. W., Yu, J., Knowles, E., Djurovic, S., Melle, I., Sundet, K., Christoforou, A., Reinvang, I., Derosse, P., Lundervold, A. J., Steen, V. M., Espeseth, T., Räikkönen, K., Widen, E., Palotie, A., Eriksson, J. G., Giegling, I., Konte, B., ... 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