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 Roussos; Stella 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

doi:10.1017/thg.2018.46

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 Roussos

Stella 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

Institute of Mental Health
BrainWorkup, LLC
The Zucker Hillside Hospital
Yale University School of Medicine
Oslo University Hospital
University of Bergen
University of Oslo
Haukeland University Hospital
University of Helsinki
Wellcome Trust
Helsinki University Central Hospital
Finnish Institute for Health and Welfare - THL
Folkhälsan
University of Halle
Icahn School of Medicine at Mount Sinai
Clinical Center (VISN 2)
University of Crete
Brigham and Women's Hospital
University of Manchester
University of Manchester
Duke University Medical Center
Department of Neurology
Imperial College London
Human Longevity Inc
University of Toronto
Eginition Hospital
University Mental Health Research Institute
Theodor-Theohari Cozzika Foundation
The Johns Hopkins University School of Medicine
University of California
Yale University
Stanford University
University of Oregon
23andMe Inc.
Duke University
National Institute of Mental Health Intramural Research Program
Johns Hopkins University
Trinity College Dublin
University of Colorado Boulder
The Hofstra North Shore–Long Island Jewish School of Medicine
Laboratory of Developmental Erythropoiesis

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

3 Citations (Scopus)

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 language	English
Pages (from-to)	394-397
Number of pages	4
Journal	Twin Research and Human Genetics
Volume	21
Issue number	5
DOIs	https://doi.org/10.1017/thg.2018.46
Publication status	Published - 1 Oct 2018

Keywords

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

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10.1017/thg.2018.46

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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

@article{269c9f3700274e02a69094c5af6464f5,

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

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'.",

keywords = "Calcium channel, Cerebellum, Gene expression, General cognitive ability, Gwas, Neurodevelopment, Nootropics, Potassium channel, Synapse",

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

note = "Publisher Copyright: {\textcopyright} The Author(s) 2018{\^A}.",

year = "2018",

month = oct,

day = "1",

doi = "10.1017/thg.2018.46",

language = "English",

volume = "21",

pages = "394--397",

journal = "Twin Research and Human Genetics",

issn = "1832-4274",

publisher = "Cambridge University Press",

number = "5",

}

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 2018, 'Multi-Trait analysis of gwas and biological insights into cognition: A response to hill (2018)', Twin Research and Human Genetics, vol. 21, no. 5, pp. 394-397. https://doi.org/10.1017/thg.2018.46

TY - JOUR

T1 - Multi-Trait analysis of gwas and biological insights into cognition

T2 - A response to hill (2018)

AU - Lam, Max

AU - Trampush, Joey W.

AU - Yu, Jin

AU - Knowles, Emma

AU - Djurovic, Srdjan

AU - Melle, Ingrid

AU - Sundet, Kjetil

AU - Christoforou, Andrea

AU - Reinvang, Ivar

AU - Derosse, Pamela

AU - Lundervold, Astri J.

AU - Steen, Vidar M.

AU - Espeseth, Thomas

AU - Räikkönen, Katri

AU - Widen, Elisabeth

AU - Palotie, Aarno

AU - Eriksson, Johan G.

AU - Giegling, Ina

AU - Konte, Bettina

AU - Roussos, Panos

AU - Giakoumaki, Stella

AU - Burdick, Katherine E.

AU - Payton, Antony

AU - Ollier, William

AU - Chiba-Falek, Ornit

AU - Attix, Deborah K.

AU - Need, Anna C.

AU - Cirulli, Elizabeth T.

AU - Voineskos, Aristotle N.

AU - Stefanis, Nikos C.

AU - Avramopoulos, Dimitrios

AU - Hatzimanolis, Alex

AU - Arking, Dan E.

AU - Smyrnis, Nikolaos

AU - Bilder, Robert M.

AU - Freimer, Nelson A.

AU - Cannon, Tyrone D.

AU - London, Edythe

AU - Poldrack, Russell A.

AU - Sabb, Fred W.

AU - Congdon, Eliza

AU - Conley, Emily Drabant

AU - Scult, Matthew A.

AU - Dickinson, Dwight

AU - Straub, Richard E.

AU - Donohoe, Gary

AU - Morris, Derek

AU - Corvin, Aiden

AU - Gill, Michael

AU - Hariri, Ahmad R.

AU - Weinberger, Daniel R.

AU - Pendleton, Neil

AU - Bitsios, Panos

AU - Rujescu, Dan

AU - Lahti, Jari

AU - Hellard, Stephanie Le

AU - Keller, Matthew C.

AU - Andreassen, Ole A.

AU - Glahn, David C.

AU - Malhotra, Anil K.

AU - Lencz, Todd

PY - 2018/10/1

Y1 - 2018/10/1

N2 - 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'.

AB - 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'.

KW - Calcium channel

KW - Cerebellum

KW - Gene expression

KW - General cognitive ability

KW - Gwas

KW - Neurodevelopment

KW - Nootropics

KW - Potassium channel

KW - Synapse

UR - https://www.scopus.com/pages/publications/85049846212

U2 - 10.1017/thg.2018.46

DO - 10.1017/thg.2018.46

M3 - Article

SN - 1832-4274

VL - 21

SP - 394

EP - 397

JO - Twin Research and Human Genetics

JF - Twin Research and Human Genetics

IS - 5

ER -

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

Abstract

Keywords

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