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 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 journal › Article › peer-review

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)	1-4
Number of pages	4
Journal	Twin Research and Human Genetics
Early online date	13 Jul 2018
DOIs	https://doi.org/10.1017/thg.2018.46
Publication status	Published - 2018

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10.1017/thg.2018.46

http://www.tara.tcd.ie/bitstream/handle/2262/83844/multitrait_analysis_of_gwas_and_biological_insights_into_cognition_a_response_to_hill_2018.pdf?sequence=1

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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, 1-4. https://doi.org/10.1017/thg.2018.46

@article{54ab5ddb9a0741f7b15d169081238da9,

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'.",

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",

year = "2018",

doi = "10.1017/thg.2018.46",

language = "English",

pages = "1--4",

journal = "Twin Research and Human Genetics",

issn = "1832-4274",

publisher = "Cambridge University Press",

}

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, pp. 1-4. 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

Y1 - 2018

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'.

U2 - 10.1017/thg.2018.46

DO - 10.1017/thg.2018.46

M3 - Article

C2 - 30001766

SN - 1832-4274

SP - 1

EP - 4

JO - Twin Research and Human Genetics

JF - Twin Research and Human Genetics

ER -

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

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