Identifying gene targets for brain-related traits using transcriptomic and methylomic data from blood

Ting Qi, Yang Wu, Jian Zeng, Futao Zhang, Angli Xue, Longda Jiang, Zhihong Zhu, Kathryn Kemper, Loic Yengo, Zhili Zheng, Mawussé Agbessi, Habibul Ahsan, Isabel Alves, Anand Andiappan, Philip Awadalla, Alexis Battle, Frank Beutner, Marc Jan Bonder, Dorret Boomsma, Mark Christiansen & 66 others Annique Claringbould, Patrick Deelen, Tõnu Esko, Marie Julie Favé, Lude Franke, Timothy Frayling, Sina Gharib, Gregory Gibson, Gibran Hemani, Rick Jansen, Mika Kähönen, Anette Kalnapenkis, Silva Kasela, Johannes Kettunen, Yungil Kim, Holger Kirsten, Peter Kovacs, Knut Krohn, Jaanika Kronberg-Guzman, Viktorija Kukushkina, Zoltan Kutalik, Bernett Lee, Terho Lehtimäki, Markus Loeffler, Urko M. Marigorta, Andres Metspalu, Lili Milani, Martina Müller-Nurasyid, Matthias Nauck, Michel Nivard, Brenda Penninx, Markus Perola, Natalia Pervjakova, Brandon Pierce, Joseph Powell, Holger Prokisch, Bruce Psaty, Olli Raitakari, Susan Ring, Samuli Ripatti, Olaf Rotzschke, Sina Ruëger, Ashis Saha, Markus Scholz, Katharina Schramm, Ilkka Seppälä, Michael Stumvoll, Patrick Sullivan, Alexander Teumer, Joachim Thiery, Lin Tong, Anke Tönjes, Jenny Van Dongen, Joyce Van Meurs, Joost Verlouw, Uwe Völker, Urmo Võsa, Hanieh Yaghootkar, Biao Zeng, Riccardo E. Marioni, Grant W. Montgomery, Ian J. Deary, Naomi R. Wray, Peter M. Visscher, Allan F. McRae, Jian Yang

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Understanding the difference in genetic regulation of gene expression between brain and blood is important for discovering genes for brain-related traits and disorders. Here, we estimate the correlation of genetic effects at the top-associated cis-expression or -DNA methylation (DNAm) quantitative trait loci (cis-eQTLs or cis-mQTLs) between brain and blood (r b ). Using publicly available data, we find that genetic effects at the top cis-eQTLs or mQTLs are highly correlated between independent brain and blood samples (r b = 0.70 for cis-eQTLs and r ^ b = 0.78 for cis-mQTLs). Using meta-analyzed brain cis-eQTL/mQTL data (n = 526 to 1194), we identify 61 genes and 167 DNAm sites associated with four brain-related phenotypes, most of which are a subset of the discoveries (97 genes and 295 DNAm sites) using data from blood with larger sample sizes (n = 1980 to 14,115). Our results demonstrate the gain of power in gene discovery for brain-related phenotypes using blood cis-eQTL/mQTL data with large sample sizes.

Original languageEnglish
Article number2282
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

Cite this

Qi, Ting ; Wu, Yang ; Zeng, Jian ; Zhang, Futao ; Xue, Angli ; Jiang, Longda ; Zhu, Zhihong ; Kemper, Kathryn ; Yengo, Loic ; Zheng, Zhili ; Agbessi, Mawussé ; Ahsan, Habibul ; Alves, Isabel ; Andiappan, Anand ; Awadalla, Philip ; Battle, Alexis ; Beutner, Frank ; Jan Bonder, Marc ; Boomsma, Dorret ; Christiansen, Mark ; Claringbould, Annique ; Deelen, Patrick ; Esko, Tõnu ; Favé, Marie Julie ; Franke, Lude ; Frayling, Timothy ; Gharib, Sina ; Gibson, Gregory ; Hemani, Gibran ; Jansen, Rick ; Kähönen, Mika ; Kalnapenkis, Anette ; Kasela, Silva ; Kettunen, Johannes ; Kim, Yungil ; Kirsten, Holger ; Kovacs, Peter ; Krohn, Knut ; Kronberg-Guzman, Jaanika ; Kukushkina, Viktorija ; Kutalik, Zoltan ; Lee, Bernett ; Lehtimäki, Terho ; Loeffler, Markus ; Marigorta, Urko M. ; Metspalu, Andres ; Milani, Lili ; Müller-Nurasyid, Martina ; Nauck, Matthias ; Nivard, Michel ; Penninx, Brenda ; Perola, Markus ; Pervjakova, Natalia ; Pierce, Brandon ; Powell, Joseph ; Prokisch, Holger ; Psaty, Bruce ; Raitakari, Olli ; Ring, Susan ; Ripatti, Samuli ; Rotzschke, Olaf ; Ruëger, Sina ; Saha, Ashis ; Scholz, Markus ; Schramm, Katharina ; Seppälä, Ilkka ; Stumvoll, Michael ; Sullivan, Patrick ; Teumer, Alexander ; Thiery, Joachim ; Tong, Lin ; Tönjes, Anke ; Van Dongen, Jenny ; Van Meurs, Joyce ; Verlouw, Joost ; Völker, Uwe ; Võsa, Urmo ; Yaghootkar, Hanieh ; Zeng, Biao ; Marioni, Riccardo E. ; Montgomery, Grant W. ; Deary, Ian J. ; Wray, Naomi R. ; Visscher, Peter M. ; McRae, Allan F. ; Yang, Jian. / Identifying gene targets for brain-related traits using transcriptomic and methylomic data from blood. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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title = "Identifying gene targets for brain-related traits using transcriptomic and methylomic data from blood",
abstract = "Understanding the difference in genetic regulation of gene expression between brain and blood is important for discovering genes for brain-related traits and disorders. Here, we estimate the correlation of genetic effects at the top-associated cis-expression or -DNA methylation (DNAm) quantitative trait loci (cis-eQTLs or cis-mQTLs) between brain and blood (r b ). Using publicly available data, we find that genetic effects at the top cis-eQTLs or mQTLs are highly correlated between independent brain and blood samples (r b = 0.70 for cis-eQTLs and r ^ b = 0.78 for cis-mQTLs). Using meta-analyzed brain cis-eQTL/mQTL data (n = 526 to 1194), we identify 61 genes and 167 DNAm sites associated with four brain-related phenotypes, most of which are a subset of the discoveries (97 genes and 295 DNAm sites) using data from blood with larger sample sizes (n = 1980 to 14,115). Our results demonstrate the gain of power in gene discovery for brain-related phenotypes using blood cis-eQTL/mQTL data with large sample sizes.",
author = "Ting Qi and Yang Wu and Jian Zeng and Futao Zhang and Angli Xue and Longda Jiang and Zhihong Zhu and Kathryn Kemper and Loic Yengo and Zhili Zheng and Mawuss{\'e} Agbessi and Habibul Ahsan and Isabel Alves and Anand Andiappan and Philip Awadalla and Alexis Battle and Frank Beutner and {Jan Bonder}, Marc and Dorret Boomsma and Mark Christiansen and Annique Claringbould and Patrick Deelen and T{\~o}nu Esko and Fav{\'e}, {Marie Julie} and Lude Franke and Timothy Frayling and Sina Gharib and Gregory Gibson and Gibran Hemani and Rick Jansen and Mika K{\"a}h{\"o}nen and Anette Kalnapenkis and Silva Kasela and Johannes Kettunen and Yungil Kim and Holger Kirsten and Peter Kovacs and Knut Krohn and Jaanika Kronberg-Guzman and Viktorija Kukushkina and Zoltan Kutalik and Bernett Lee and Terho Lehtim{\"a}ki and Markus Loeffler and Marigorta, {Urko M.} and Andres Metspalu and Lili Milani and Martina M{\"u}ller-Nurasyid and Matthias Nauck and Michel Nivard and Brenda Penninx and Markus Perola and Natalia Pervjakova and Brandon Pierce and Joseph Powell and Holger Prokisch and Bruce Psaty and Olli Raitakari and Susan Ring and Samuli Ripatti and Olaf Rotzschke and Sina Ru{\"e}ger and Ashis Saha and Markus Scholz and Katharina Schramm and Ilkka Sepp{\"a}l{\"a} and Michael Stumvoll and Patrick Sullivan and Alexander Teumer and Joachim Thiery and Lin Tong and Anke T{\"o}njes and {Van Dongen}, Jenny and {Van Meurs}, Joyce and Joost Verlouw and Uwe V{\"o}lker and Urmo V{\~o}sa and Hanieh Yaghootkar and Biao Zeng and Marioni, {Riccardo E.} and Montgomery, {Grant W.} and Deary, {Ian J.} and Wray, {Naomi R.} and Visscher, {Peter M.} and McRae, {Allan F.} and Jian Yang",
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Qi, T, Wu, Y, Zeng, J, Zhang, F, Xue, A, Jiang, L, Zhu, Z, Kemper, K, Yengo, L, Zheng, Z, Agbessi, M, Ahsan, H, Alves, I, Andiappan, A, Awadalla, P, Battle, A, Beutner, F, Jan Bonder, M, Boomsma, D, Christiansen, M, Claringbould, A, Deelen, P, Esko, T, Favé, MJ, Franke, L, Frayling, T, Gharib, S, Gibson, G, Hemani, G, Jansen, R, Kähönen, M, Kalnapenkis, A, Kasela, S, Kettunen, J, Kim, Y, Kirsten, H, Kovacs, P, Krohn, K, Kronberg-Guzman, J, Kukushkina, V, Kutalik, Z, Lee, B, Lehtimäki, T, Loeffler, M, Marigorta, UM, Metspalu, A, Milani, L, Müller-Nurasyid, M, Nauck, M, Nivard, M, Penninx, B, Perola, M, Pervjakova, N, Pierce, B, Powell, J, Prokisch, H, Psaty, B, Raitakari, O, Ring, S, Ripatti, S, Rotzschke, O, Ruëger, S, Saha, A, Scholz, M, Schramm, K, Seppälä, I, Stumvoll, M, Sullivan, P, Teumer, A, Thiery, J, Tong, L, Tönjes, A, Van Dongen, J, Van Meurs, J, Verlouw, J, Völker, U, Võsa, U, Yaghootkar, H, Zeng, B, Marioni, RE, Montgomery, GW, Deary, IJ, Wray, NR, Visscher, PM, McRae, AF & Yang, J 2018, 'Identifying gene targets for brain-related traits using transcriptomic and methylomic data from blood' Nature Communications, vol. 9, no. 1, 2282. https://doi.org/10.1038/s41467-018-04558-1

Identifying gene targets for brain-related traits using transcriptomic and methylomic data from blood. / Qi, Ting; Wu, Yang; Zeng, Jian; Zhang, Futao; Xue, Angli; Jiang, Longda; Zhu, Zhihong; Kemper, Kathryn; Yengo, Loic; Zheng, Zhili; Agbessi, Mawussé; Ahsan, Habibul; Alves, Isabel; Andiappan, Anand; Awadalla, Philip; Battle, Alexis; Beutner, Frank; Jan Bonder, Marc; Boomsma, Dorret; Christiansen, Mark; Claringbould, Annique; Deelen, Patrick; Esko, Tõnu; Favé, Marie Julie; Franke, Lude; Frayling, Timothy; Gharib, Sina; Gibson, Gregory; Hemani, Gibran; Jansen, Rick; Kähönen, Mika; Kalnapenkis, Anette; Kasela, Silva; Kettunen, Johannes; Kim, Yungil; Kirsten, Holger; Kovacs, Peter; Krohn, Knut; Kronberg-Guzman, Jaanika; Kukushkina, Viktorija; Kutalik, Zoltan; Lee, Bernett; Lehtimäki, Terho; Loeffler, Markus; Marigorta, Urko M.; Metspalu, Andres; Milani, Lili; Müller-Nurasyid, Martina; Nauck, Matthias; Nivard, Michel; Penninx, Brenda; Perola, Markus; Pervjakova, Natalia; Pierce, Brandon; Powell, Joseph; Prokisch, Holger; Psaty, Bruce; Raitakari, Olli; Ring, Susan; Ripatti, Samuli; Rotzschke, Olaf; Ruëger, Sina; Saha, Ashis; Scholz, Markus; Schramm, Katharina; Seppälä, Ilkka; Stumvoll, Michael; Sullivan, Patrick; Teumer, Alexander; Thiery, Joachim; Tong, Lin; Tönjes, Anke; Van Dongen, Jenny; Van Meurs, Joyce; Verlouw, Joost; Völker, Uwe; Võsa, Urmo; Yaghootkar, Hanieh; Zeng, Biao; Marioni, Riccardo E.; Montgomery, Grant W.; Deary, Ian J.; Wray, Naomi R.; Visscher, Peter M.; McRae, Allan F.; Yang, Jian.

In: Nature Communications, Vol. 9, No. 1, 2282, 01.12.2018.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Identifying gene targets for brain-related traits using transcriptomic and methylomic data from blood

AU - Qi, Ting

AU - Wu, Yang

AU - Zeng, Jian

AU - Zhang, Futao

AU - Xue, Angli

AU - Jiang, Longda

AU - Zhu, Zhihong

AU - Kemper, Kathryn

AU - Yengo, Loic

AU - Zheng, Zhili

AU - Agbessi, Mawussé

AU - Ahsan, Habibul

AU - Alves, Isabel

AU - Andiappan, Anand

AU - Awadalla, Philip

AU - Battle, Alexis

AU - Beutner, Frank

AU - Jan Bonder, Marc

AU - Boomsma, Dorret

AU - Christiansen, Mark

AU - Claringbould, Annique

AU - Deelen, Patrick

AU - Esko, Tõnu

AU - Favé, Marie Julie

AU - Franke, Lude

AU - Frayling, Timothy

AU - Gharib, Sina

AU - Gibson, Gregory

AU - Hemani, Gibran

AU - Jansen, Rick

AU - Kähönen, Mika

AU - Kalnapenkis, Anette

AU - Kasela, Silva

AU - Kettunen, Johannes

AU - Kim, Yungil

AU - Kirsten, Holger

AU - Kovacs, Peter

AU - Krohn, Knut

AU - Kronberg-Guzman, Jaanika

AU - Kukushkina, Viktorija

AU - Kutalik, Zoltan

AU - Lee, Bernett

AU - Lehtimäki, Terho

AU - Loeffler, Markus

AU - Marigorta, Urko M.

AU - Metspalu, Andres

AU - Milani, Lili

AU - Müller-Nurasyid, Martina

AU - Nauck, Matthias

AU - Nivard, Michel

AU - Penninx, Brenda

AU - Perola, Markus

AU - Pervjakova, Natalia

AU - Pierce, Brandon

AU - Powell, Joseph

AU - Prokisch, Holger

AU - Psaty, Bruce

AU - Raitakari, Olli

AU - Ring, Susan

AU - Ripatti, Samuli

AU - Rotzschke, Olaf

AU - Ruëger, Sina

AU - Saha, Ashis

AU - Scholz, Markus

AU - Schramm, Katharina

AU - Seppälä, Ilkka

AU - Stumvoll, Michael

AU - Sullivan, Patrick

AU - Teumer, Alexander

AU - Thiery, Joachim

AU - Tong, Lin

AU - Tönjes, Anke

AU - Van Dongen, Jenny

AU - Van Meurs, Joyce

AU - Verlouw, Joost

AU - Völker, Uwe

AU - Võsa, Urmo

AU - Yaghootkar, Hanieh

AU - Zeng, Biao

AU - Marioni, Riccardo E.

AU - Montgomery, Grant W.

AU - Deary, Ian J.

AU - Wray, Naomi R.

AU - Visscher, Peter M.

AU - McRae, Allan F.

AU - Yang, Jian

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Understanding the difference in genetic regulation of gene expression between brain and blood is important for discovering genes for brain-related traits and disorders. Here, we estimate the correlation of genetic effects at the top-associated cis-expression or -DNA methylation (DNAm) quantitative trait loci (cis-eQTLs or cis-mQTLs) between brain and blood (r b ). Using publicly available data, we find that genetic effects at the top cis-eQTLs or mQTLs are highly correlated between independent brain and blood samples (r b = 0.70 for cis-eQTLs and r ^ b = 0.78 for cis-mQTLs). Using meta-analyzed brain cis-eQTL/mQTL data (n = 526 to 1194), we identify 61 genes and 167 DNAm sites associated with four brain-related phenotypes, most of which are a subset of the discoveries (97 genes and 295 DNAm sites) using data from blood with larger sample sizes (n = 1980 to 14,115). Our results demonstrate the gain of power in gene discovery for brain-related phenotypes using blood cis-eQTL/mQTL data with large sample sizes.

AB - Understanding the difference in genetic regulation of gene expression between brain and blood is important for discovering genes for brain-related traits and disorders. Here, we estimate the correlation of genetic effects at the top-associated cis-expression or -DNA methylation (DNAm) quantitative trait loci (cis-eQTLs or cis-mQTLs) between brain and blood (r b ). Using publicly available data, we find that genetic effects at the top cis-eQTLs or mQTLs are highly correlated between independent brain and blood samples (r b = 0.70 for cis-eQTLs and r ^ b = 0.78 for cis-mQTLs). Using meta-analyzed brain cis-eQTL/mQTL data (n = 526 to 1194), we identify 61 genes and 167 DNAm sites associated with four brain-related phenotypes, most of which are a subset of the discoveries (97 genes and 295 DNAm sites) using data from blood with larger sample sizes (n = 1980 to 14,115). Our results demonstrate the gain of power in gene discovery for brain-related phenotypes using blood cis-eQTL/mQTL data with large sample sizes.

UR - http://www.scopus.com/inward/record.url?scp=85048415370&partnerID=8YFLogxK

U2 - 10.1038/s41467-018-04558-1

DO - 10.1038/s41467-018-04558-1

M3 - Article

VL - 9

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 2282

ER -