The Genetic Architecture of the Human Immune System: A Bioresource for Autoimmunity and Disease Pathogenesis

Mario Roederer; Lydia Quaye; Massimo Mangino; Margaret H Beddall; Yolanda Mahnke; Pratip Chattopadhyay; Isabella Tosi; Luca Napolitano; Manuela Terranova Barberio; Cristina Menni; Federica Villanova; Paola Di Meglio; Tim D Spector; Frank O Nestle

doi:10.1016/j.cell.2015.02.046

The Genetic Architecture of the Human Immune System: A Bioresource for Autoimmunity and Disease Pathogenesis

Mario Roederer, Lydia Quaye, Massimo Mangino, Margaret H Beddall, Yolanda Mahnke, Pratip Chattopadhyay, Isabella Tosi, Luca Napolitano, Manuela Terranova Barberio, Cristina Menni, Federica Villanova, Paola Di Meglio, Tim D Spector, Frank O Nestle

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Abstract

Despite recent discoveries of genetic variants associated with autoimmunity and infection, genetic control of the human immune system during homeostasis is poorly understood. We undertook a comprehensive immunophenotyping approach, analyzing 78,000 immune traits in 669 female twins. From the top 151 heritable traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP associations at 11 genetic loci, explaining up to 36% of the variation of 19 traits. We found multiple associations with canonical traits of all major immune cell subsets and uncovered insights into genetic control for regulatory T cells. This data set also revealed traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease. Our data establish a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases, providing a shortcut to identifying potential mechanisms of immune-related diseases.

Original language	English
Pages (from-to)	387-403
Number of pages	17
Journal	Cell
Volume	161
Issue number	2
Early online date	12 Mar 2015
DOIs	https://doi.org/10.1016/j.cell.2015.02.046
Publication status	Published - 9 Apr 2015

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10.1016/j.cell.2015.02.046

The genetic architecture of the_ROEDERER_Accepted 4Feb2015_GREEN AAM
© 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
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Roederer, M., Quaye, L., Mangino, M., Beddall, M. H., Mahnke, Y., Chattopadhyay, P., Tosi, I., Napolitano, L., Terranova Barberio, M., Menni, C., Villanova, F., Di Meglio, P., Spector, T. D., & Nestle, F. O. (2015). The Genetic Architecture of the Human Immune System: A Bioresource for Autoimmunity and Disease Pathogenesis. Cell, 161(2), 387-403. https://doi.org/10.1016/j.cell.2015.02.046

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title = "The Genetic Architecture of the Human Immune System: A Bioresource for Autoimmunity and Disease Pathogenesis",

abstract = "Despite recent discoveries of genetic variants associated with autoimmunity and infection, genetic control of the human immune system during homeostasis is poorly understood. We undertook a comprehensive immunophenotyping approach, analyzing 78,000 immune traits in 669 female twins. From the top 151 heritable traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP associations at 11 genetic loci, explaining up to 36% of the variation of 19 traits. We found multiple associations with canonical traits of all major immune cell subsets and uncovered insights into genetic control for regulatory T cells. This data set also revealed traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease. Our data establish a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases, providing a shortcut to identifying potential mechanisms of immune-related diseases.",

author = "Mario Roederer and Lydia Quaye and Massimo Mangino and Beddall, {Margaret H} and Yolanda Mahnke and Pratip Chattopadhyay and Isabella Tosi and Luca Napolitano and {Terranova Barberio}, Manuela and Cristina Menni and Federica Villanova and {Di Meglio}, Paola and Spector, {Tim D} and Nestle, {Frank O}",

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Roederer, M, Quaye, L, Mangino, M, Beddall, MH, Mahnke, Y, Chattopadhyay, P, Tosi, I, Napolitano, L , Terranova Barberio, M , Menni, C , Villanova, F , Di Meglio, P , Spector, TD & Nestle, FO 2015, 'The Genetic Architecture of the Human Immune System: A Bioresource for Autoimmunity and Disease Pathogenesis', Cell, vol. 161, no. 2, pp. 387-403. https://doi.org/10.1016/j.cell.2015.02.046

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T2 - A Bioresource for Autoimmunity and Disease Pathogenesis

AU - Roederer, Mario

AU - Quaye, Lydia

AU - Mangino, Massimo

AU - Beddall, Margaret H

AU - Mahnke, Yolanda

AU - Chattopadhyay, Pratip

AU - Tosi, Isabella

AU - Napolitano, Luca

AU - Terranova Barberio, Manuela

AU - Menni, Cristina

AU - Villanova, Federica

AU - Di Meglio, Paola

AU - Spector, Tim D

AU - Nestle, Frank O

PY - 2015/4/9

Y1 - 2015/4/9

N2 - Despite recent discoveries of genetic variants associated with autoimmunity and infection, genetic control of the human immune system during homeostasis is poorly understood. We undertook a comprehensive immunophenotyping approach, analyzing 78,000 immune traits in 669 female twins. From the top 151 heritable traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP associations at 11 genetic loci, explaining up to 36% of the variation of 19 traits. We found multiple associations with canonical traits of all major immune cell subsets and uncovered insights into genetic control for regulatory T cells. This data set also revealed traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease. Our data establish a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases, providing a shortcut to identifying potential mechanisms of immune-related diseases.

AB - Despite recent discoveries of genetic variants associated with autoimmunity and infection, genetic control of the human immune system during homeostasis is poorly understood. We undertook a comprehensive immunophenotyping approach, analyzing 78,000 immune traits in 669 female twins. From the top 151 heritable traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP associations at 11 genetic loci, explaining up to 36% of the variation of 19 traits. We found multiple associations with canonical traits of all major immune cell subsets and uncovered insights into genetic control for regulatory T cells. This data set also revealed traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease. Our data establish a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases, providing a shortcut to identifying potential mechanisms of immune-related diseases.

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DO - 10.1016/j.cell.2015.02.046

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VL - 161

SP - 387

EP - 403

JO - Cell

JF - Cell

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The Genetic Architecture of the Human Immune System: A Bioresource for Autoimmunity and Disease Pathogenesis

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