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Mapping cis- and trans-regulatory effects across multiple tissues in twins
Open accessAbstract
Sequence-based variation in gene expression is a key driver of disease risk. Common variants regulating expression in cis have been mapped in many expression quantitative trait locus (eQTL) studies, typically in single tissues from unrelated individuals. Here, we present a comprehensive analysis of gene expression across multiple tissues conducted in a large set of mono- and dizygotic twins that allows systematic dissection of genetic (cis and trans) and non-genetic effects on gene expression. Using identity-by-descent estimates, we show that at least 40% of the total heritable cis effect on expression cannot be accounted for by common cis variants, a finding that reveals the contribution of low-frequency and rare regulatory variants with respect to both transcriptional regulation and complex trait susceptibility. We show that a substantial proportion of gene expression heritability is trans to the structural gene, and we identify several replicating trans variants that act predominantly in a tissue-restricted manner and may regulate the transcription of many genes.
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“Previous studies have evaluated the association between variation and transcript expression in humans (1-3).”
From Impact of regulatory variation from RNA to protein (2015) · cites this paper as [3]
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Cites
Statistical significance for genomewide studies
Storey, J. D., & Tibshirani, R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1530509100 · Cited by 9,692
Merlin—rapid analysis of dense genetic maps using sparse gene flow trees
Abecasis, G. R., Cherny, S. S., Cookson, W., & Cardon, L. R. (2001) · Nature Genetics · doi:10.1038/ng786 · Cited by 3,323
Mapping short DNA sequencing reads and calling variants using mapping quality scores
Li, H., Ruan, J., & Durbin, R. (2008) · Genome Research · doi:10.1101/gr.078212.108 · Cited by 2,638
Self-citationMaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes
Li, Y., Willer, C. J., Ding, J., Scheet, P., & Abecasis, G. R. (2010) · Genetic Epidemiology · doi:10.1002/gepi.20533 · Cited by 1,843
GenABEL: an R library for genome-wide association analysis
Aulchenko, Y. S., Ripke, S., Isaacs, A., & van Duijn, C. M. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm108 · Cited by 1,836
Missing heritability and strategies for finding the underlying causes of complex disease
Eichler, E. E., Flint, J., Gibson, G. C., Kong, A., Leal, S. M., Moore, J. H., & Nadeau, J. H. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2809 · Cited by 1,728
Self-citationALSPAC–The Avon Longitudinal Study of Parents and Children
Golding, Pembrey, Jones, & The Alspac Study Team (2001) · Paediatric and Perinatal Epidemiology · doi:10.1046/j.1365-3016.2001.00325.x · Cited by 1,549
Genetics of gene expression and its effect on disease
Emilsson, V., Thorleifsson, G., Zhang, B., Leonardson, A. S., Zink, F., Zhu, J., Carlson, S., Helgason, A., Walters, G. B., Gunnarsdottir, S., et al. (2008) · Nature · doi:10.1038/nature06758 · Cited by 1,296
Self-citationPopulation genomics of human gene expression
Stranger, B. E., Nica, A. C., Forrest, M. S., Dimas, A. S., Bird, C., Beazley, C., Ingle, C., Dunning, M., Flicek, P., Koller, D., et al. (2007) · Nature Genetics · doi:10.1038/ng2142 · Cited by 1,151
Self-citationThe Fine-Scale Structure of Recombination Rate Variation in the Human Genome
McVean, G., Myers, S., Hunt, S. E., Deloukas, P., Bentley, D., & Donnelly, P. (2004) · Science · doi:10.1126/science.1092500 · Cited by 989
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Additional file 9 of DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures
Gomez-Alonso, M. D. C., Kretschmer, A., Wilson, R., Pfeiffer, L., Karhunen, V., Seppälä, I., Zhang, W., Mittelstraß, K., Wahl, S., Matías‐García, P. R., et al. (2021) · Figshare · doi:10.6084/m9.figshare.13545125
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Additional file 17 of DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures
Gomez-Alonso, M. D. C., Kretschmer, A., Wilson, R., Pfeiffer, L., Karhunen, V., Seppälä, I., Zhang, W., Mittelstraß, K., Wahl, S., Matías‐García, P. R., et al. (2021) · Figshare · doi:10.6084/m9.figshare.13545089
Additional file 1 of DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures
Gomez-Alonso, M. D. C., Kretschmer, A., Wilson, R., Pfeiffer, L., Karhunen, V., Seppälä, I., Zhang, W., Mittelstraß, K., Wahl, S., Matías‐García, P. R., et al. (2021) · Figshare · doi:10.6084/m9.figshare.13545098
Additional file 15 of DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures
Gomez-Alonso, M. D. C., Kretschmer, A., Wilson, R., Pfeiffer, L., Karhunen, V., Seppälä, I., Zhang, W., Mittelstraß, K., Wahl, S., Matías‐García, P. R., et al. (2021) · Figshare · doi:10.6084/m9.figshare.13545083
Additional file 16 of DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures
Gomez-Alonso, M. D. C., Kretschmer, A., Wilson, R., Pfeiffer, L., Karhunen, V., Seppälä, I., Zhang, W., Mittelstraß, K., Wahl, S., Matías‐García, P. R., et al. (2021) · Figshare · doi:10.6084/m9.figshare.13545086
Liu, S., Won, H., Clarke, D., Matoba, N., Khullar, S., Mu, Y., Wang, D., & Gerstein, M. (2022) · Figshare · doi:10.6084/m9.figshare.21622719
Additional file 14 of DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures
Gomez-Alonso, M. D. C., Kretschmer, A., Wilson, R., Pfeiffer, L., Karhunen, V., Seppälä, I., Zhang, W., Mittelstraß, K., Wahl, S., Matías‐García, P. R., et al. (2021) · Figshare · doi:10.6084/m9.figshare.13545080
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Additional file 2 of DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures
Gomez-Alonso, M. D. C., Kretschmer, A., Wilson, R., Pfeiffer, L., Karhunen, V., Seppälä, I., Zhang, W., Mittelstraß, K., Wahl, S., Matías‐García, P. R., et al. (2021) · Figshare · doi:10.6084/m9.figshare.13545104
Additional file 3 of DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures
Gomez-Alonso, M. D. C., Kretschmer, A., Wilson, R., Pfeiffer, L., Karhunen, V., Seppälä, I., Zhang, W., Mittelstraß, K., Wahl, S., Matías‐García, P. R., et al. (2021) · Figshare · doi:10.6084/m9.figshare.13545107
Additional file 11 of DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures
Gomez-Alonso, M. D. C., Kretschmer, A., Wilson, R., Pfeiffer, L., Karhunen, V., Seppälä, I., Zhang, W., Mittelstraß, K., Wahl, S., Matías‐García, P. R., et al. (2021) · Figshare · doi:10.6084/m9.figshare.13545071
Additional file 12 of DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures
Gomez-Alonso, M. D. C., Kretschmer, A., Wilson, R., Pfeiffer, L., Karhunen, V., Seppälä, I., Zhang, W., Mittelstraß, K., Wahl, S., Matías‐García, P. R., et al. (2021) · Figshare · doi:10.6084/m9.figshare.13545074
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Żyła, J., López-Riego, M., O’Brien, G., Finnon, P., Kaprio, J. A., Polańska, J., & Badie, C. (2025) · Gene Reports · doi:10.1016/j.genrep.2025.102142
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Baer, L., Lardelli, M. T., & Pederson, S. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.02.11.637777
Shen, X., & Liu, Z. (2025) · medRxiv · doi:10.1101/2025.03.19.25324051
Gu, J., Fuller, C., Carbonetto, P. S., He, X., Zheng, J., & Li, H. (2025) · eLife · doi:10.7554/elife.107957
Gu, J., Fuller, C., Carbonetto, P. S., He, X., Zheng, J., & Li, H. (2025) · eLife · doi:10.7554/elife.107957.1
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Additional file 6 of DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures
Gomez-Alonso, M. D. C., Kretschmer, A., Wilson, R., Pfeiffer, L., Karhunen, V., Seppälä, I., Zhang, W., Mittelstraß, K., Wahl, S., Matías‐García, P. R., et al. (2021) · Figshare · doi:10.6084/m9.figshare.13545116
Additional file 8 of DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures
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Christiansen, C., Tomlinson, M., Eliot, M., Nilsson, E., Costeira, R., Xia, Y., Villicaña, S., Mompeó, O., Wells, P. M., Castillo-Fernandez, J., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20330218
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Additional file 7 of DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures
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Kim, D. J., Lim, J. E., Jung, H.-U., Chung, J. Y., Baek, E. J., Jung, H., Kwon, S. Y., Kim, H. K., Kang, J.-O., Park, K., et al. (2024) · Figshare · doi:10.6084/m9.figshare.24432122
Additional file 4 of DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures
Gomez-Alonso, M. D. C., Kretschmer, A., Wilson, R., Pfeiffer, L., Karhunen, V., Seppälä, I., Zhang, W., Mittelstraß, K., Wahl, S., Matías‐García, P. R., et al. (2021) · Figshare · doi:10.6084/m9.figshare.13545110
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Dong, Z., Ma, Y., Zhou, H., Shi, L., Ye, G., Yang, L., Liu, P., & Zhou, L. (2020) · Figshare · doi:10.6084/m9.figshare.13106280
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Christiansen, C., Tomlinson, M., Eliot, M., Nilsson, E., Costeira, R., Xia, Y., Villicaña, S., Mompeó, O., Wells, P. M., Castillo-Fernandez, J., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20330221
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Metadata
- Authors
- The Multiple Tissue Human Expression Resource (MuTHER) Consortium, Grundberg, E., Small, K. S., Hedman, Å. K., Nica, A. C., Buil, A., Keildson, S., Bell, J. T., Yang, T.-P., Meduri, E., Barrett, A., Nisbett, J., Sekowska, M., Wilk, A., Shin, S.-Y., Glass, D., Travers, M., Min, J. L., Ring, S., Ho, K., Thorleifsson, G., Kong, A., Thorsteindottir, U., Ainali, C., Dimas, A. S., Hassanali, N., Ingle, C., Knowles, D., Krestyaninova, M., Lowe, C. E., Di Meglio, P., Montgomery, S. B., Parts, L., Potter, S., Surdulescu, G., Tsaprouni, L., Tsoka, S., Bataille, V., Durbin, R., Nestle, F. O., O'Rahilly, S., Soranzo, N., Lindgren, C. M., Zondervan, K. T., Ahmadi, K. R., Schadt, E. E., Stefansson, K., Smith, G. D., McCarthy, M. I., Deloukas, P., Dermitzakis, E. T., & Spector, T. D.
- Affiliations
- King's College London (GB)
- Centre for Human Genetics (GB)
- University of Geneva (CH)
- Wellcome Sanger Institute (GB)
- Churchill Hospital (GB)
- University of Bristol (GB)
- deCODE Genetics (Iceland) (IS)
- University of Cambridge (GB)
- European Bioinformatics Institute (GB)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- McCarthy, Mark I
- Deloukas, Panos
- Dermitzakis, Emmanouil T
- Spector, Tim D
- ORCID
- Grundberg, Elin
- Small, Kerrin S
- Hedman, Åsa K
- Buil, Alfonso
- Bell, Jordana T
- Yang, Tsun-Po
- Meduri, Eshwar
- Sekowska, Magdalena
- Shin, So-Youn
- Glass, Daniel
- Min, Josine L
- Ho, Karen
- Kong, Augustine
- Ainali, Chrysanthi
- Dimas, Antigone S
- Knowles, David
- Krestyaninova, Maria
- Lowe, Christopher E
- Montgomery, Stephen B
- Parts, Leopold
- Tsaprouni, Loukia
- Tsoka, Sophia
- Bataille, Veronique
- Durbin, Richard
- Nestle, Frank O
- Soranzo, Nicole
- Lindgren, Cecilia M
- Zondervan, Krina T
- Ahmadi, Kourosh R
- Schadt, Eric E
- Smith, George Davey
- McCarthy, Mark I
- Deloukas, Panos
- Dermitzakis, Emmanouil T
- Spector, Tim D
- Venue
- Nature Genetics
- Published
- 2012-09-02
- Volume
- 44
- Issue
- 10
- Pages
- 1084-1089
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC3784328
- OpenAlex
- W2019232525
- Cited by
- 729
- References
- 44
- Citations by year
- 2026: 8 · 2025: 21 · 2024: 15 · 2023: 26 · 2022: 40 · 2021: 41 · 2020: 47 · 2019: 58 · 2018: 52 · 2017: 87 · 2016: 88 · 2015: 94 · 2014: 86 · 2013: 59 · 2012: 5
- FWCI
- 47.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- BCU Open Access Repository (Birmingham City University) (submittedVersion)
- Funders
- National Science Foundation (FP7/2007-2013)
- Wellcome Trust (FP7/2007–2013, 095515, 081917/Z/07/Z, 085235, 092731, 090532)
- Louis-Jeantet Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (FP7/2007-2013, 201413)
- National Institutes of Health (FP7/2007-2013)
- National Institute of Mental Health (HEALTH-F4-2007-201413, R01MH090941)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- heritability of gene expression, cis-regulatory effects, monozygotic twins, dizygotic twins, expression quantitative trait loci, identity by descent, low-frequency variants, tissue-specific gene expression
- MeSH terms
- Adult, Aged, Aged, 80 and over, Chromosome Mapping, Female, Gene Expression Regulation, Humans, Genetic Linkage, Lymphocytes, Middle Aged, Models, Genetic, Organ Specificity, Skin, Transcription, Genetic, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Subcutaneous Fat, Gene-Environment Interaction
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