Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes

Towfique Raj; Katie Rothamel; Sara Mostafavi; Chun Ye; Mark N. Lee; Joseph M. Replogle; Ting Feng; Michelle Lee; Natasha Asinovski; Irene Frohlich; Selina Imboywa; Alina Von Korff; Yukinori Okada; Nikolaos A. Patsopoulos; Scott Davis; Cristin McCabe; Hyun Il Paik; Gyan P. Srivastava; Soumya Raychaudhuri; David A. Hafler; Daphne Koller; Aviv Regev; Nir Hacohen; Diane Mathis; Christophe Benoist; Barbara E. Stranger; Philip L. De Jager

doi:10.1126/science.1249547

Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes

Towfique Raj, Katie Rothamel, Sara Mostafavi, Chun Ye, Mark N. Lee, Joseph M. Replogle, Ting Feng, Michelle Lee, Natasha Asinovski, Irene Frohlich, Selina Imboywa, Alina Von Korff, Yukinori Okada, Nikolaos A. Patsopoulos, Scott Davis, Cristin McCabe, Hyun Il Paik, Gyan P. Srivastava, Soumya Raychaudhuri, David A. HaflerDaphne Koller, Aviv Regev, Nir Hacohen, Diane Mathis, Christophe Benoist, Barbara E. Stranger, Philip L. De Jager

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

370 Scopus citations

Abstract

To extend our understanding of the genetic basis of human immune function and dysfunction, we performed an expression quantitative trait locus (eQTL) study of purified CD4⁺ T cells and monocytes, representing adaptive and innate immunity, in a multi-ethnic cohort of 461 healthy individuals. Context-specific cis- and trans-eQTLs were identified, and cross-population mapping allowed, in some cases, putative functional assignment of candidate causal regulatory variants for disease-associated loci. We note an over-representation of T cell-specific eQTLs among susceptibility alleles for autoimmune diseases and of monocyte-specific eQTLs among Alzheimer's and Parkinson's disease variants. This polarization implicates specific immune cell types in these diseases and points to the need to identify the cell-autonomous effects of disease susceptibility variants.

Original language	English
Pages (from-to)	519-523
Number of pages	5
Journal	Science
Volume	344
Issue number	6183
DOIs	https://doi.org/10.1126/science.1249547
State	Published - 2014
Externally published	Yes

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Raj, T., Rothamel, K., Mostafavi, S., Ye, C., Lee, M. N., Replogle, J. M., Feng, T., Lee, M., Asinovski, N., Frohlich, I., Imboywa, S., Von Korff, A., Okada, Y., Patsopoulos, N. A., Davis, S., McCabe, C., Paik, H. I., Srivastava, G. P., Raychaudhuri, S., ... De Jager, P. L. (2014). Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes. Science, 344(6183), 519-523. https://doi.org/10.1126/science.1249547

@article{174181f71af44f7ab099ccde9a11c0ed,

title = "Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes",

abstract = "To extend our understanding of the genetic basis of human immune function and dysfunction, we performed an expression quantitative trait locus (eQTL) study of purified CD4+ T cells and monocytes, representing adaptive and innate immunity, in a multi-ethnic cohort of 461 healthy individuals. Context-specific cis- and trans-eQTLs were identified, and cross-population mapping allowed, in some cases, putative functional assignment of candidate causal regulatory variants for disease-associated loci. We note an over-representation of T cell-specific eQTLs among susceptibility alleles for autoimmune diseases and of monocyte-specific eQTLs among Alzheimer's and Parkinson's disease variants. This polarization implicates specific immune cell types in these diseases and points to the need to identify the cell-autonomous effects of disease susceptibility variants.",

author = "Towfique Raj and Katie Rothamel and Sara Mostafavi and Chun Ye and Lee, {Mark N.} and Replogle, {Joseph M.} and Ting Feng and Michelle Lee and Natasha Asinovski and Irene Frohlich and Selina Imboywa and {Von Korff}, Alina and Yukinori Okada and Patsopoulos, {Nikolaos A.} and Scott Davis and Cristin McCabe and Paik, {Hyun Il} and Srivastava, {Gyan P.} and Soumya Raychaudhuri and Hafler, {David A.} and Daphne Koller and Aviv Regev and Nir Hacohen and Diane Mathis and Christophe Benoist and Stranger, {Barbara E.} and {De Jager}, {Philip L.}",

year = "2014",

doi = "10.1126/science.1249547",

language = "English",

volume = "344",

pages = "519--523",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6183",

}

Raj, T, Rothamel, K, Mostafavi, S, Ye, C, Lee, MN, Replogle, JM, Feng, T, Lee, M, Asinovski, N, Frohlich, I, Imboywa, S, Von Korff, A, Okada, Y, Patsopoulos, NA, Davis, S, McCabe, C, Paik, HI, Srivastava, GP, Raychaudhuri, S, Hafler, DA, Koller, D, Regev, A, Hacohen, N, Mathis, D, Benoist, C, Stranger, BE & De Jager, PL 2014, 'Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes', Science, vol. 344, no. 6183, pp. 519-523. https://doi.org/10.1126/science.1249547

TY - JOUR

T1 - Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes

AU - Raj, Towfique

AU - Rothamel, Katie

AU - Mostafavi, Sara

AU - Ye, Chun

AU - Lee, Mark N.

AU - Replogle, Joseph M.

AU - Feng, Ting

AU - Lee, Michelle

AU - Asinovski, Natasha

AU - Frohlich, Irene

AU - Imboywa, Selina

AU - Von Korff, Alina

AU - Okada, Yukinori

AU - Patsopoulos, Nikolaos A.

AU - Davis, Scott

AU - McCabe, Cristin

AU - Paik, Hyun Il

AU - Srivastava, Gyan P.

AU - Raychaudhuri, Soumya

AU - Hafler, David A.

AU - Koller, Daphne

AU - Regev, Aviv

AU - Hacohen, Nir

AU - Mathis, Diane

AU - Benoist, Christophe

AU - Stranger, Barbara E.

AU - De Jager, Philip L.

PY - 2014

Y1 - 2014

N2 - To extend our understanding of the genetic basis of human immune function and dysfunction, we performed an expression quantitative trait locus (eQTL) study of purified CD4+ T cells and monocytes, representing adaptive and innate immunity, in a multi-ethnic cohort of 461 healthy individuals. Context-specific cis- and trans-eQTLs were identified, and cross-population mapping allowed, in some cases, putative functional assignment of candidate causal regulatory variants for disease-associated loci. We note an over-representation of T cell-specific eQTLs among susceptibility alleles for autoimmune diseases and of monocyte-specific eQTLs among Alzheimer's and Parkinson's disease variants. This polarization implicates specific immune cell types in these diseases and points to the need to identify the cell-autonomous effects of disease susceptibility variants.

AB - To extend our understanding of the genetic basis of human immune function and dysfunction, we performed an expression quantitative trait locus (eQTL) study of purified CD4+ T cells and monocytes, representing adaptive and innate immunity, in a multi-ethnic cohort of 461 healthy individuals. Context-specific cis- and trans-eQTLs were identified, and cross-population mapping allowed, in some cases, putative functional assignment of candidate causal regulatory variants for disease-associated loci. We note an over-representation of T cell-specific eQTLs among susceptibility alleles for autoimmune diseases and of monocyte-specific eQTLs among Alzheimer's and Parkinson's disease variants. This polarization implicates specific immune cell types in these diseases and points to the need to identify the cell-autonomous effects of disease susceptibility variants.

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DO - 10.1126/science.1249547

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AN - SCOPUS:84900338300

SN - 0036-8075

VL - 344

SP - 519

EP - 523

JO - Science

JF - Science

IS - 6183

ER -

Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes

Abstract

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