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Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity

Natural Killer cells are innate lymphocytes with central roles in immunosurveillance and are implicated in autoimmune pathogenesis. The degree to which regulatory variants affect Natural Killer cell gene expression is poorly understood. Here we perform expression quantitative trait locus mapping of...

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Autores principales: Gilchrist, James J., Makino, Seiko, Naranbhai, Vivek, Sharma, Piyush K., Koturan, Surya, Tong, Orion, Taylor, Chelsea A., Watson, Robert A., de los Aires, Alba Verge, Cooper, Rosalin, Lau, Evelyn, Danielli, Sara, Hameiri-Bowen, Dan, Lee, Wanseon, Ng, Esther, Whalley, Justin, Knight, Julian C., Fairfax, Benjamin P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283523/
https://www.ncbi.nlm.nih.gov/pubmed/35835762
http://dx.doi.org/10.1038/s41467-022-31626-4
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author Gilchrist, James J.
Makino, Seiko
Naranbhai, Vivek
Sharma, Piyush K.
Koturan, Surya
Tong, Orion
Taylor, Chelsea A.
Watson, Robert A.
de los Aires, Alba Verge
Cooper, Rosalin
Lau, Evelyn
Danielli, Sara
Hameiri-Bowen, Dan
Lee, Wanseon
Ng, Esther
Whalley, Justin
Knight, Julian C.
Fairfax, Benjamin P.
author_facet Gilchrist, James J.
Makino, Seiko
Naranbhai, Vivek
Sharma, Piyush K.
Koturan, Surya
Tong, Orion
Taylor, Chelsea A.
Watson, Robert A.
de los Aires, Alba Verge
Cooper, Rosalin
Lau, Evelyn
Danielli, Sara
Hameiri-Bowen, Dan
Lee, Wanseon
Ng, Esther
Whalley, Justin
Knight, Julian C.
Fairfax, Benjamin P.
author_sort Gilchrist, James J.
collection PubMed
description Natural Killer cells are innate lymphocytes with central roles in immunosurveillance and are implicated in autoimmune pathogenesis. The degree to which regulatory variants affect Natural Killer cell gene expression is poorly understood. Here we perform expression quantitative trait locus mapping of negatively selected Natural Killer cells from a population of healthy Europeans (n = 245). We find a significant subset of genes demonstrate expression quantitative trait loci specific to Natural Killer cells and these are highly informative of human disease, in particular autoimmunity. A Natural Killer cell transcriptome-wide association study across five common autoimmune diseases identifies further novel associations at 27 genes. In addition to these cis observations, we find novel master-regulatory regions impacting expression of trans gene networks at regions including 19q13.4, the Killer cell Immunoglobulin-like Receptor region, GNLY, MC1R and UVSSA. Our findings provide new insights into the unique biology of Natural Killer cells, demonstrating markedly different expression quantitative trait loci from other immune cells, with implications for disease mechanisms.
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spelling pubmed-92835232022-07-16 Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity Gilchrist, James J. Makino, Seiko Naranbhai, Vivek Sharma, Piyush K. Koturan, Surya Tong, Orion Taylor, Chelsea A. Watson, Robert A. de los Aires, Alba Verge Cooper, Rosalin Lau, Evelyn Danielli, Sara Hameiri-Bowen, Dan Lee, Wanseon Ng, Esther Whalley, Justin Knight, Julian C. Fairfax, Benjamin P. Nat Commun Article Natural Killer cells are innate lymphocytes with central roles in immunosurveillance and are implicated in autoimmune pathogenesis. The degree to which regulatory variants affect Natural Killer cell gene expression is poorly understood. Here we perform expression quantitative trait locus mapping of negatively selected Natural Killer cells from a population of healthy Europeans (n = 245). We find a significant subset of genes demonstrate expression quantitative trait loci specific to Natural Killer cells and these are highly informative of human disease, in particular autoimmunity. A Natural Killer cell transcriptome-wide association study across five common autoimmune diseases identifies further novel associations at 27 genes. In addition to these cis observations, we find novel master-regulatory regions impacting expression of trans gene networks at regions including 19q13.4, the Killer cell Immunoglobulin-like Receptor region, GNLY, MC1R and UVSSA. Our findings provide new insights into the unique biology of Natural Killer cells, demonstrating markedly different expression quantitative trait loci from other immune cells, with implications for disease mechanisms. Nature Publishing Group UK 2022-07-14 /pmc/articles/PMC9283523/ /pubmed/35835762 http://dx.doi.org/10.1038/s41467-022-31626-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Gilchrist, James J.
Makino, Seiko
Naranbhai, Vivek
Sharma, Piyush K.
Koturan, Surya
Tong, Orion
Taylor, Chelsea A.
Watson, Robert A.
de los Aires, Alba Verge
Cooper, Rosalin
Lau, Evelyn
Danielli, Sara
Hameiri-Bowen, Dan
Lee, Wanseon
Ng, Esther
Whalley, Justin
Knight, Julian C.
Fairfax, Benjamin P.
Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity
title Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity
title_full Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity
title_fullStr Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity
title_full_unstemmed Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity
title_short Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity
title_sort natural killer cells demonstrate distinct eqtl and transcriptome-wide disease associations, highlighting their role in autoimmunity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283523/
https://www.ncbi.nlm.nih.gov/pubmed/35835762
http://dx.doi.org/10.1038/s41467-022-31626-4
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