Cell Specific eQTL Analysis without Sorting Cells

HJ Westra; D Arends; T Esko; Marjolein Peters; C Schurmann; K Schramm; J Kettunen; H Yaghootkar; BP Fairfax; AK Andiappan; Y Li; JY Fu; J Karjalainen; M Platteel; M Visschedijk; RK Weersma; S Kasela; L Milani; L Tserel; P Peterson; E Reinmaa; Bert Hofman; André Uitterlinden; Fernando Rivadeneira; G Homuth; A Petersmann; R Lorbeer; H Prokisch; T Meitinger; Cindy Herder; M Roden; H Grallert; S Ripatti; M Perola; AR Wood; D Melzer; L Ferrucci; AB Singleton; DG Hernandez; JC Knight; R Melchiotti; B Lee; M Poidinger; F Zolezzi; A Larbi; DY Wang; LH van den Berg; JH Veldink; O Rotzschke; S Makino; V Salomaa; K Strauch; U Volker; Joyce van Meurs; A Metspalu; C Wijmenga; RC Jansen; L Franke

doi:10.1371/journal.pgen.1005223

Cell Specific eQTL Analysis without Sorting Cells

HJ Westra, D Arends, T Esko, Marjolein Peters, C Schurmann, K Schramm, J Kettunen, H Yaghootkar, BP Fairfax, AK Andiappan, Y Li, JY Fu, J Karjalainen, M Platteel, M Visschedijk, RK Weersma, S Kasela, L Milani, L Tserel, P PetersonE Reinmaa, Bert Hofman, André Uitterlinden, Fernando Rivadeneira, G Homuth, A Petersmann, R Lorbeer, H Prokisch, T Meitinger, Cindy Herder, M Roden, H Grallert, S Ripatti, M Perola, AR Wood, D Melzer, L Ferrucci, AB Singleton, DG Hernandez, JC Knight, R Melchiotti, B Lee, M Poidinger, F Zolezzi, A Larbi, DY Wang, LH van den Berg, JH Veldink, O Rotzschke, S Makino, V Salomaa, K Strauch, U Volker, Joyce van Meurs, A Metspalu, C Wijmenga, RC Jansen, L Franke

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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	Undefined/Unknown
Journal	PLoS Genetics (print)
Volume	11
Issue number	5
DOIs	https://doi.org/10.1371/journal.pgen.1005223
Publication status	Published - 2015

Research programs

EMC MM-01-39-09-A
EMC NIHES-01-64-02

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10.1371/journal.pgen.1005223

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Cite this

Westra, HJ., Arends, D., Esko, T., Peters, M., Schurmann, C., Schramm, K., Kettunen, J., Yaghootkar, H., Fairfax, BP., Andiappan, AK., Li, Y., Fu, JY., Karjalainen, J., Platteel, M., Visschedijk, M., Weersma, RK., Kasela, S., Milani, L., Tserel, L., ... Franke, L. (2015). Cell Specific eQTL Analysis without Sorting Cells. PLoS Genetics (print), 11(5). https://doi.org/10.1371/journal.pgen.1005223

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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.",

author = "HJ Westra and D Arends and T Esko and Marjolein Peters and C Schurmann and K Schramm and J Kettunen and H Yaghootkar and BP Fairfax and AK Andiappan and Y Li and JY Fu and J Karjalainen and M Platteel and M Visschedijk and RK Weersma and S Kasela and L Milani and L Tserel and P Peterson and E Reinmaa and Bert Hofman and Andr{\'e} Uitterlinden and Fernando Rivadeneira and G Homuth and A Petersmann and R Lorbeer and H Prokisch and T Meitinger and Cindy Herder and M Roden and H Grallert and S Ripatti and M Perola and AR Wood and D Melzer and L Ferrucci and AB Singleton and DG Hernandez and JC Knight and R Melchiotti and B Lee and M Poidinger and F Zolezzi and A Larbi and DY Wang and {van den Berg}, LH and JH Veldink and O Rotzschke and S Makino and V Salomaa and K Strauch and U Volker and {van Meurs}, Joyce and A Metspalu and C Wijmenga and RC Jansen and L Franke",

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Westra, HJ, Arends, D, Esko, T, Peters, M, Schurmann, C, Schramm, K, Kettunen, J, Yaghootkar, H, Fairfax, BP, Andiappan, AK, Li, Y, Fu, JY, Karjalainen, J, Platteel, M, Visschedijk, M, Weersma, RK, Kasela, S, Milani, L, Tserel, L, Peterson, P, Reinmaa, E, Hofman, B , Uitterlinden, A , 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, Volker, U, van Meurs, J, Metspalu, A, Wijmenga, C, Jansen, RC & Franke, L 2015, 'Cell Specific eQTL Analysis without Sorting Cells', PLoS Genetics (print), vol. 11, no. 5. https://doi.org/10.1371/journal.pgen.1005223

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T1 - Cell Specific eQTL Analysis without Sorting Cells

AU - Westra, HJ

AU - Arends, D

AU - Esko, T

AU - Peters, Marjolein

AU - Schurmann, C

AU - Schramm, K

AU - Kettunen, J

AU - Yaghootkar, H

AU - Fairfax, BP

AU - Andiappan, AK

AU - Li, Y

AU - Fu, JY

AU - Karjalainen, J

AU - Platteel, M

AU - Visschedijk, M

AU - Weersma, RK

AU - Kasela, S

AU - Milani, L

AU - Tserel, L

AU - Peterson, P

AU - Reinmaa, E

AU - Hofman, Bert

AU - Uitterlinden, André

AU - Rivadeneira, Fernando

AU - Homuth, G

AU - Petersmann, A

AU - Lorbeer, R

AU - Prokisch, H

AU - Meitinger, T

AU - Herder, Cindy

AU - Roden, M

AU - Grallert, H

AU - Ripatti, S

AU - Perola, M

AU - Wood, AR

AU - Melzer, D

AU - Ferrucci, L

AU - Singleton, AB

AU - Hernandez, DG

AU - Knight, JC

AU - Melchiotti, R

AU - Lee, B

AU - Poidinger, M

AU - Zolezzi, F

AU - Larbi, A

AU - Wang, DY

AU - van den Berg, LH

AU - Veldink, JH

AU - Rotzschke, O

AU - Makino, S

AU - Salomaa, V

AU - Strauch, K

AU - Volker, U

AU - van Meurs, Joyce

AU - Metspalu, A

AU - Wijmenga, C

AU - Jansen, RC

AU - Franke, L

PY - 2015

Y1 - 2015

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.

U2 - 10.1371/journal.pgen.1005223

DO - 10.1371/journal.pgen.1005223

M3 - Article

C2 - 25955312

SN - 1553-7390

VL - 11

JO - PLoS Genetics (print)

JF - PLoS Genetics (print)

IS - 5

ER -