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 (rb). 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 (\[\hat r_b = 0.70\] for cis-eQTLs and \[\hat r_ b = 0.78\] 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.

Details

Title
Identifying gene targets for brain-related traits using transcriptomic and methylomic data from blood
Author
Ting Qi 1   VIAFID ORCID Logo  ; Wu, Yang 1   VIAFID ORCID Logo  ; Zeng, Jian 1   VIAFID ORCID Logo  ; Zhang, Futao 2 ; Xue, Angli 1 ; Jiang, Longda 1 ; Zhu, Zhihong 1 ; Kemper, Kathryn 1   VIAFID ORCID Logo  ; Yengo, Loic 1 ; Zheng, Zhili 3 ; Agbessi, Mawussé 4 ; Ahsan, Habibul 5 ; Alves, Isabel 4 ; Andiappan, Anand 6 ; Awadalla, Philip 4 ; Battle, Alexis 7 ; Beutner, Frank 8 ; Bonder, Marc Jan 9 ; Boomsma, Dorret 10 ; Christiansen, Mark 11 ; Claringbould, Annique 9 ; Deelen, Patrick 9 ; Tõnu Esko 12 ; Marie-Julie Favé 4 ; Franke, Lude 9 ; Frayling, Timothy 13 ; Gharib, Sina 14 ; Gibson, Gregory 15 ; Gibran Hemani 16 ; Jansen, Rick 10 ; Kähönen, Mika 17 ; Kalnapenkis, Anette 12 ; Silva Kasela 12 ; Kettunen, Johannes 18 ; Kim, Yungil 7 ; Kirsten, Holger 19 ; Kovacs, Peter 20 ; Krohn, Knut 21 ; Kronberg-Guzman, Jaanika 12 ; Kukushkina, Viktorija 12 ; Kutalik, Zoltan 22 ; Lee, Bernett 6 ; Lehtimäki, Terho 23 ; Loeffler, Markus 24 ; Marigorta, Urko M 15 ; Metspalu, Andres 12 ; Milani, Lili 12 ; Müller-Nurasyid, Martina 25 ; Nauck, Matthias 26 ; Nivard, Michel 10 ; Penninx, Brenda 10 ; Perola, Markus 18 ; Pervjakova, Natalia 12 ; Pierce, Brandon 5 ; Powell, Joseph 1 ; Prokisch, Holger 27 ; Psaty, Bruce 28 ; Raitakari, Olli 29 ; Ring, Susan 30 ; Ripatti, Samuli 18 ; Rotzschke, Olaf 6 ; Ruëger, Sina 22 ; Saha, Ashis 7 ; Scholz, Markus 24 ; Schramm, Katharina 25 ; Seppälä, Ilkka 23 ; Stumvoll, Michael 20 ; Sullivan, Patrick 31 ; Teumer, Alexander 32 ; Thiery, Joachim 33 ; Lin, Tong 5 ; Tönjes, Anke 34 ; Jenny van Dongen 10 ; Joyce van Meurs 35 ; Verlouw, Joost 35 ; Völker, Uwe 36 ; Võsa, Urmo 9 ; Yaghootkar, Hanieh 13 ; Zeng, Biao 15 ; Marioni, Riccardo E 37 ; Montgomery, Grant W 1   VIAFID ORCID Logo  ; Deary, Ian J 38 ; Wray, Naomi R 2   VIAFID ORCID Logo  ; Visscher, Peter M 2   VIAFID ORCID Logo  ; McRae, Allan F 1   VIAFID ORCID Logo  ; Yang, Jian 39   VIAFID ORCID Logo 

 Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia 
 Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia; Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia 
 Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia; The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China 
 Computational Biology, Ontario Institute for Cancer Research, Toronto, ON, Canada 
 Department of Public Health Sciences, University of Chicago, Chicago, IL, USA 
 Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore 
 Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA 
 Heart Center Leipzig, Universität Leipzig, Leipzig, Germany 
 Department of Genetics, University Medical Centre Groningen, Groningen, The Netherlands 
10  Faculty of Genes, Behavior and Health, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands 
11  Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA 
12  Estonian Genome Center, University of Tartu, Tartu, Estonia 
13  Exeter Medical School, University of Exeter, Exeter, UK 
14  Department of Medicine, University of Washington, Seattle, WA, USA 
15  School of Biological Sciences, Georgia Tech, Atlanta, GA, USA 
16  MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK 
17  Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland; Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland 
18  National Institute for Health and Welfare, University of Helsinki, Helsinki, Finland 
19  Institute für Medizinische InformatiK, Statistik und Epidemiologie, LIFE–Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany 
20  IFB Adiposity Diseases, Department of Medicine, Universität Leipzig, Leipzig, Germany 
21  Interdisciplinary Center for Clinical Research, Faculty of Medicine, Universität Leipzig, Leipzig, Germany 
22  Lausanne University Hospital, Lausanne, Switzerland 
23  Department of Clinical Chemistry, Fimlab Laboratories and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland 
24  Institut für Medizinische InformatiK, Statistik und Epidemiologie, LIFE–Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany 
25  Institute of Genetic Epidemiology, Helmholtz Zentrum München, München, Germany 
26  Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany 
27  Institute of Human Genetics, Helmholtz Zentrum München, München, Germany 
28  Cardiovascular Health Research Unit, Departments of Epidemiology, Medicine, and Health Services, University of Washington, Seattle, WA, USA 
29  Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland; University of Turku, Turku, Finland 
30  School of Social and Community Medicine, University of Bristol, Bristol, UK 
31  Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Solna, Sweden 
32  Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany 
33  Institute for Laboratory Medicine, LIFE–Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany 
34  Division of Endocrinology and Nephrology, Department of Medicine, Universität Leipzig, Leipzig, Germany 
35  Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands 
36  Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany 
37  Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK; Department of Psychology, Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK 
38  Department of Psychology, Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK 
39  Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia; Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia; The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China 
Pages
1-12
Publication year
2018
Publication date
Jun 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2053307712
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.