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; Riccardo E. Marioni; Grant W. Montgomery; Ian J. Deary; Naomi R. Wray; Peter M. Visscher; Allan F. Mcrae; Jian Yang

doi:10.1038/s41467-018-04558-1

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, Riccardo E. Marioni, Grant W. Montgomery, Ian J. Deary, Naomi R. Wray, Peter M. Visscher, Allan F. Mcrae, Jian Yang

Research output: Contribution to journal › Article › peer-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 (rˆb=0.70 for cis-eQTLs and rˆb=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 language	English
Article number	2282
Pages (from-to)	1-12
Journal	Nature Communications
Volume	9
Issue number	1
Early online date	11 Jun 2018
DOIs	https://doi.org/10.1038/s41467-018-04558-1
Publication status	Published - 11 Jun 2018

Keywords

DNA methylation
gene regulation
genetics of the nervous system
genome-wide association studies

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4 Finished

Brain imaging and cognitive ageing in the Lothian Birth Cohort 1936: III
Wardlaw, J., Bastin, M. & Deary, I.
MRC
1/05/15 → 30/04/19
Project: Research
RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.
Deary, I., Gale, C., Holmes, M., Logie, P., Maclullich, A., Porteous, D., Seckl, J., Starr, J., Wardlaw, J. & Okely, J.
1/09/13 → 31/08/19
Project: Research
A Hundred at Ninety: the common cause Hypothesis of Ageing tested in four waves of the Lothian Birth Cohort 1921
Deary, I., Bates, T., Gow, A. & Starr, J.
UK central government bodies/local authorities, health and hospital authorities
1/01/11 → 31/12/12
Project: Research

Cite this

Qi, T., Wu, Y., Zeng, J., Zhang, F., Xue, A., Jiang, L., Zhu, Z., Kemper, K., Yengo, L., Zheng, Z., Marioni, R. E., Montgomery, G. W., Deary, I. J., Wray, N. R., Visscher, P. M., Mcrae, A. F., & Yang, J. (2018). Identifying gene targets for brain-related traits using transcriptomic and methylomic data from blood. Nature Communications, 9(1), 1-12. [2282]. https://doi.org/10.1038/s41467-018-04558-1

Qi, Ting ; Wu, Yang ; Zeng, Jian ; Zhang, Futao ; Xue, Angli ; Jiang, Longda ; Zhu, Zhihong ; Kemper, Kathryn ; Yengo, Loic ; Zheng, Zhili ; 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. pp. 1-12.

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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 (rˆb=0.70 for cis-eQTLs and rˆb=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.",

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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 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, 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, pp. 1-12. 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; 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, 11.06.2018, p. 1-12.

Research output: Contribution to journal › Article › peer-review

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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 - 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

N1 - GOLD OA

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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 (rˆb=0.70 for cis-eQTLs and rˆb=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.

KW - DNA methylation

KW - gene regulation

KW - genetics of the nervous system

KW - genome-wide association studies

U2 - 10.1038/s41467-018-04558-1

DO - 10.1038/s41467-018-04558-1

M3 - Article

VL - 9

SP - 1

EP - 12

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 2282

ER -

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

Abstract

Keywords

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Projects

Brain imaging and cognitive ageing in the Lothian Birth Cohort 1936: III

RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.

A Hundred at Ninety: the common cause Hypothesis of Ageing tested in four waves of the Lothian Birth Cohort 1921

Cite this