Cell Specific eQTL Analysis without Sorting Cells

Harm-Jan Westra; Danny Arends; Tonu Esko; Marjolein J. Peters; Claudia Schurmann; Katharina Schramm; Johannes Kettunen; Hanieh Yaghootkar; Benjamin P. Fairfax; Anand Kumar Andiappan; Yang Li; Jingyuan Fu; Juha Karjalainen; Mathieu Platteel; Marijn Visschedijk; Rinse K. Weersma; Silva Kasela; Lili Milani; Liina Tserel; Part Peterson; Eva Reinmaa; Albert Hofman; Andre G. Uitterlinden; Fernando Rivadeneira; Georg Homuth; Astrid Petersmann; Roberto Lorbeer; Holger Prokisch; Thomas Meitinger; Christian Herder; Michael Roden; Harald Grallert; Samuli Ripatti; Markus Perola; Andrew R. Wood; David Melzer; Luigi Ferrucci; Andrew B. Singleton; Dena G. Hernandez; Julian C. Knight; Rossella Melchiotti; Bernett Lee; Michael Poidinger; Francesca Zolezzi; Anis Larbi; De Yun Wang; Leonard H. van den Berg; Jan H. Veldink; Olaf Rotzschke; Seiko Makino; Veikko Salomaa; Konstantin Strauch; Uwe Voelker; Joyce B. J. van Meurs; Andres Metspalu; Cisca Wijmenga; Ritsert C. Jansen; Lude Franke

doi:10.1371/journal.pgen.1005223

Cell Specific eQTL Analysis without Sorting Cells

Harm-Jan Westra^*, Danny Arends, Tonu Esko, Marjolein J. Peters, Claudia Schurmann, Katharina Schramm, Johannes Kettunen, Hanieh Yaghootkar, Benjamin P. Fairfax, Anand Kumar Andiappan, Yang Li, Jingyuan Fu, Juha Karjalainen, Mathieu Platteel, Marijn Visschedijk, Rinse K. Weersma, Silva Kasela, Lili Milani, Liina Tserel, Part PetersonEva Reinmaa, Albert Hofman, Andre G. Uitterlinden, Fernando Rivadeneira, Georg Homuth, Astrid Petersmann, Roberto Lorbeer, Holger Prokisch, Thomas Meitinger, Christian Herder, Michael Roden, Harald Grallert, Samuli Ripatti, Markus Perola, Andrew R. Wood, David Melzer, Luigi Ferrucci, Andrew B. Singleton, Dena G. Hernandez, Julian C. Knight, Rossella Melchiotti, Bernett Lee, Michael Poidinger, Francesca Zolezzi, Anis Larbi, De Yun Wang, Leonard H. van den Berg, Jan H. Veldink, Olaf Rotzschke, Seiko Makino, Veikko Salomaa, Konstantin Strauch, Uwe Voelker, Joyce B. J. van Meurs, Andres Metspalu, Cisca Wijmenga, Ritsert C. Jansen, Lude Franke

^*Corresponding author for this work

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

53 Citations (Scopus)

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Abstract

The functional consequences of trait associated SNPs are often investigated using expression quantitative trait locus (eQTL) mapping. While trait-associated variants may operate in a cell-type specific manner, eQTL datasets for such cell-types may not always be available. We performed a genome-environment interaction (GxE) meta-analysis on data from 5,683 samples to infer the cell type specificity of whole blood cis-eQTLs. We demonstrate that this method is able to predict neutrophil and lymphocyte specific cis-eQTLs and replicate these predictions in independent cell-type specific datasets. Finally, we show that SNPs associated with Crohn's disease preferentially affect gene expression within neutrophils, including the archetypal NOD2 locus.

Original language	English
Article number	1005223
Number of pages	17
Journal	PLoS genetics
Volume	11
Issue number	5
DOIs	https://doi.org/10.1371/journal.pgen.1005223
Publication status	Published - May-2015

Keywords

ACTIVE CROHNS-DISEASE
GENE-EXPRESSION
WIDE ASSOCIATION
DNA METHYLATION
VARIANTS
HETEROGENEITY
BLOOD

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Cell Specific eQTL Analysis without Sorting CellsFinal publisher's version, 1.12 MBLicence: CC BY

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Westra, H-J., Arends, D., Esko, T., Peters, M. J., Schurmann, C., Schramm, K., Kettunen, J., Yaghootkar, H., Fairfax, B. P., Andiappan, A. K., Li, Y., Fu, J., Karjalainen, J., Platteel, M., Visschedijk, M., Weersma, R. K., Kasela, S., Milani, L., Tserel, L., ... Franke, L. (2015). Cell Specific eQTL Analysis without Sorting Cells. PLoS genetics, 11(5), [1005223]. https://doi.org/10.1371/journal.pgen.1005223

Westra, Harm-Jan ; Arends, Danny ; Esko, Tonu ; Peters, Marjolein J. ; Schurmann, Claudia ; Schramm, Katharina ; Kettunen, Johannes ; Yaghootkar, Hanieh ; Fairfax, Benjamin P. ; Andiappan, Anand Kumar ; Li, Yang ; Fu, Jingyuan ; Karjalainen, Juha ; Platteel, Mathieu ; Visschedijk, Marijn ; Weersma, Rinse K. ; Kasela, Silva ; Milani, Lili ; Tserel, Liina ; Peterson, Part ; Reinmaa, Eva ; Hofman, Albert ; Uitterlinden, Andre G. ; Rivadeneira, Fernando ; Homuth, Georg ; Petersmann, Astrid ; Lorbeer, Roberto ; Prokisch, Holger ; Meitinger, Thomas ; Herder, Christian ; Roden, Michael ; Grallert, Harald ; Ripatti, Samuli ; Perola, Markus ; Wood, Andrew R. ; Melzer, David ; Ferrucci, Luigi ; Singleton, Andrew B. ; Hernandez, Dena G. ; Knight, Julian C. ; Melchiotti, Rossella ; Lee, Bernett ; Poidinger, Michael ; Zolezzi, Francesca ; Larbi, Anis ; Wang, De Yun ; van den Berg, Leonard H. ; Veldink, Jan H. ; Rotzschke, Olaf ; Makino, Seiko ; Salomaa, Veikko ; Strauch, Konstantin ; Voelker, Uwe ; van Meurs, Joyce B. J. ; Metspalu, Andres ; Wijmenga, Cisca ; Jansen, Ritsert C. ; Franke, Lude. / Cell Specific eQTL Analysis without Sorting Cells. In: PLoS genetics. 2015 ; Vol. 11, No. 5.

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title = "Cell Specific eQTL Analysis without Sorting Cells",

abstract = "The functional consequences of trait associated SNPs are often investigated using expression quantitative trait locus (eQTL) mapping. While trait-associated variants may operate in a cell-type specific manner, eQTL datasets for such cell-types may not always be available. We performed a genome-environment interaction (GxE) meta-analysis on data from 5,683 samples to infer the cell type specificity of whole blood cis-eQTLs. We demonstrate that this method is able to predict neutrophil and lymphocyte specific cis-eQTLs and replicate these predictions in independent cell-type specific datasets. Finally, we show that SNPs associated with Crohn's disease preferentially affect gene expression within neutrophils, including the archetypal NOD2 locus.",

keywords = "ACTIVE CROHNS-DISEASE, GENE-EXPRESSION, WIDE ASSOCIATION, DNA METHYLATION, VARIANTS, HETEROGENEITY, BLOOD",

author = "Harm-Jan Westra and Danny Arends and Tonu Esko and Peters, {Marjolein J.} and Claudia Schurmann and Katharina Schramm and Johannes Kettunen and Hanieh Yaghootkar and Fairfax, {Benjamin P.} and Andiappan, {Anand Kumar} and Yang Li and Jingyuan Fu and Juha Karjalainen and Mathieu Platteel and Marijn Visschedijk and Weersma, {Rinse K.} and Silva Kasela and Lili Milani and Liina Tserel and Part Peterson and Eva Reinmaa and Albert Hofman and Uitterlinden, {Andre G.} and Fernando Rivadeneira and Georg Homuth and Astrid Petersmann and Roberto Lorbeer and Holger Prokisch and Thomas Meitinger and Christian Herder and Michael Roden and Harald Grallert and Samuli Ripatti and Markus Perola and Wood, {Andrew R.} and David Melzer and Luigi Ferrucci and Singleton, {Andrew B.} and Hernandez, {Dena G.} and Knight, {Julian C.} and Rossella Melchiotti and Bernett Lee and Michael Poidinger and Francesca Zolezzi and Anis Larbi and Wang, {De Yun} and {van den Berg}, {Leonard H.} and Veldink, {Jan H.} and Olaf Rotzschke and Seiko Makino and Veikko Salomaa and Konstantin Strauch and Uwe Voelker and {van Meurs}, {Joyce B. J.} and Andres Metspalu and Cisca Wijmenga and Jansen, {Ritsert C.} and Lude Franke",

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doi = "10.1371/journal.pgen.1005223",

language = "English",

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journal = "PLoS genetics",

issn = "1553-7390",

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Westra, H-J, Arends, D, Esko, T, Peters, MJ, Schurmann, C, Schramm, K, Kettunen, J, Yaghootkar, H, Fairfax, BP, Andiappan, AK, Li, Y , Fu, J, Karjalainen, J, Platteel, M , Visschedijk, M , Weersma, RK, Kasela, S, Milani, L, Tserel, L, Peterson, P, Reinmaa, E, Hofman, A, Uitterlinden, AG, Rivadeneira, F, Homuth, G, Petersmann, A, Lorbeer, R, Prokisch, H, Meitinger, T, Herder, C, Roden, M, Grallert, H, Ripatti, S, Perola, M, Wood, AR, Melzer, D, Ferrucci, L, Singleton, AB, Hernandez, DG, Knight, JC, Melchiotti, R, Lee, B, Poidinger, M, Zolezzi, F, Larbi, A, Wang, DY, van den Berg, LH, Veldink, JH, Rotzschke, O, Makino, S, Salomaa, V, Strauch, K, Voelker, U, van Meurs, JBJ, Metspalu, A, Wijmenga, C , Jansen, RC & Franke, L 2015, 'Cell Specific eQTL Analysis without Sorting Cells', PLoS genetics, vol. 11, no. 5, 1005223. https://doi.org/10.1371/journal.pgen.1005223

Cell Specific eQTL Analysis without Sorting Cells. / Westra, Harm-Jan; Arends, Danny; Esko, Tonu; Peters, Marjolein J.; Schurmann, Claudia; Schramm, Katharina; Kettunen, Johannes; Yaghootkar, Hanieh; Fairfax, Benjamin P.; Andiappan, Anand Kumar; Li, Yang ; Fu, Jingyuan; Karjalainen, Juha; Platteel, Mathieu ; Visschedijk, Marijn ; Weersma, Rinse K.; Kasela, Silva; Milani, Lili; Tserel, Liina; Peterson, Part; Reinmaa, Eva; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Homuth, Georg; Petersmann, Astrid; Lorbeer, Roberto; Prokisch, Holger; Meitinger, Thomas; Herder, Christian; Roden, Michael; Grallert, Harald; Ripatti, Samuli; Perola, Markus; Wood, Andrew R.; Melzer, David; Ferrucci, Luigi; Singleton, Andrew B.; Hernandez, Dena G.; Knight, Julian C.; Melchiotti, Rossella; Lee, Bernett; Poidinger, Michael; Zolezzi, Francesca; Larbi, Anis; Wang, De Yun; van den Berg, Leonard H.; Veldink, Jan H.; Rotzschke, Olaf; Makino, Seiko; Salomaa, Veikko; Strauch, Konstantin; Voelker, Uwe; van Meurs, Joyce B. J.; Metspalu, Andres; Wijmenga, Cisca ; Jansen, Ritsert C.; Franke, Lude.

In: PLoS genetics, Vol. 11, No. 5, 1005223, 05.2015.

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

TY - JOUR

T1 - Cell Specific eQTL Analysis without Sorting Cells

AU - Westra, Harm-Jan

AU - Arends, Danny

AU - Esko, Tonu

AU - Peters, Marjolein J.

AU - Schurmann, Claudia

AU - Schramm, Katharina

AU - Kettunen, Johannes

AU - Yaghootkar, Hanieh

AU - Fairfax, Benjamin P.

AU - Andiappan, Anand Kumar

AU - Li, Yang

AU - Fu, Jingyuan

AU - Karjalainen, Juha

AU - Platteel, Mathieu

AU - Visschedijk, Marijn

AU - Weersma, Rinse K.

AU - Kasela, Silva

AU - Milani, Lili

AU - Tserel, Liina

AU - Peterson, Part

AU - Reinmaa, Eva

AU - Hofman, Albert

AU - Uitterlinden, Andre G.

AU - Rivadeneira, Fernando

AU - Homuth, Georg

AU - Petersmann, Astrid

AU - Lorbeer, Roberto

AU - Prokisch, Holger

AU - Meitinger, Thomas

AU - Herder, Christian

AU - Roden, Michael

AU - Grallert, Harald

AU - Ripatti, Samuli

AU - Perola, Markus

AU - Wood, Andrew R.

AU - Melzer, David

AU - Ferrucci, Luigi

AU - Singleton, Andrew B.

AU - Hernandez, Dena G.

AU - Knight, Julian C.

AU - Melchiotti, Rossella

AU - Lee, Bernett

AU - Poidinger, Michael

AU - Zolezzi, Francesca

AU - Larbi, Anis

AU - Wang, De Yun

AU - van den Berg, Leonard H.

AU - Veldink, Jan H.

AU - Rotzschke, Olaf

AU - Makino, Seiko

AU - Salomaa, Veikko

AU - Strauch, Konstantin

AU - Voelker, Uwe

AU - van Meurs, Joyce B. J.

AU - Metspalu, Andres

AU - Wijmenga, Cisca

AU - Jansen, Ritsert C.

AU - Franke, Lude

PY - 2015/5

Y1 - 2015/5

N2 - The functional consequences of trait associated SNPs are often investigated using expression quantitative trait locus (eQTL) mapping. While trait-associated variants may operate in a cell-type specific manner, eQTL datasets for such cell-types may not always be available. We performed a genome-environment interaction (GxE) meta-analysis on data from 5,683 samples to infer the cell type specificity of whole blood cis-eQTLs. We demonstrate that this method is able to predict neutrophil and lymphocyte specific cis-eQTLs and replicate these predictions in independent cell-type specific datasets. Finally, we show that SNPs associated with Crohn's disease preferentially affect gene expression within neutrophils, including the archetypal NOD2 locus.

AB - The functional consequences of trait associated SNPs are often investigated using expression quantitative trait locus (eQTL) mapping. While trait-associated variants may operate in a cell-type specific manner, eQTL datasets for such cell-types may not always be available. We performed a genome-environment interaction (GxE) meta-analysis on data from 5,683 samples to infer the cell type specificity of whole blood cis-eQTLs. We demonstrate that this method is able to predict neutrophil and lymphocyte specific cis-eQTLs and replicate these predictions in independent cell-type specific datasets. Finally, we show that SNPs associated with Crohn's disease preferentially affect gene expression within neutrophils, including the archetypal NOD2 locus.

KW - ACTIVE CROHNS-DISEASE

KW - GENE-EXPRESSION

KW - WIDE ASSOCIATION

KW - DNA METHYLATION

KW - VARIANTS

KW - HETEROGENEITY

KW - BLOOD

U2 - 10.1371/journal.pgen.1005223

DO - 10.1371/journal.pgen.1005223

M3 - Article

C2 - 25955312

VL - 11

JO - PLoS genetics

JF - PLoS genetics

SN - 1553-7390

IS - 5

M1 - 1005223

ER -