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.
authors.affiliation: ImmunoTechnology Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA. Electronic address: roederer@nih.gov.
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.affiliation: Department of Twin Research & Genetic Epidemiology, King's College London, London SE1 7EH, UK.
authors.forename: Lydia
authors.initials: L
authors.lastname: Quaye
authors.affiliation: Department of Twin Research & Genetic Epidemiology, King's College London, London SE1 7EH, UK; NIHR Biomedical Research Centre at Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mangino
authors.affiliation: ImmunoTechnology Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
authors.forename: Margaret H
authors.initials: MH
authors.lastname: Beddall
authors.affiliation: ImmunoTechnology Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Mahnke
authors.affiliation: ImmunoTechnology Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
authors.forename: Pratip
authors.initials: P
authors.lastname: Chattopadhyay
authors.affiliation: Cutaneous Medicine Unit, St. John's Institute of Dermatology, King's College London, London SE1 9RT, UK; NIHR Biomedical Research Centre at Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK.
authors.forename: Isabella
authors.initials: I
authors.lastname: Tosi
authors.affiliation: Cutaneous Medicine Unit, St. John's Institute of Dermatology, King's College London, London SE1 9RT, UK.
authors.forename: Luca
authors.initials: L
authors.lastname: Napolitano
authors.affiliation: Cutaneous Medicine Unit, St. John's Institute of Dermatology, King's College London, London SE1 9RT, UK.
authors.forename: Manuela
authors.initials: M
authors.lastname: Terranova Barberio
authors.affiliation: Department of Twin Research & Genetic Epidemiology, King's College London, London SE1 7EH, UK.
authors.forename: Cristina
authors.initials: C
authors.lastname: Menni
authors.affiliation: Cutaneous Medicine Unit, St. John's Institute of Dermatology, King's College London, London SE1 9RT, UK; NIHR Biomedical Research Centre at Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK.
authors.forename: Federica
authors.initials: F
authors.lastname: Villanova
authors.affiliation: Cutaneous Medicine Unit, St. John's Institute of Dermatology, King's College London, London SE1 9RT, UK.
authors.forename: Paola
authors.initials: P
authors.lastname: Di Meglio
authors.affiliation: Department of Twin Research & Genetic Epidemiology, King's College London, London SE1 7EH, UK. Electronic address: tim.spector@kcl.ac.uk.
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: Cutaneous Medicine Unit, St. John's Institute of Dermatology, King's College London, London SE1 9RT, UK; NIHR Biomedical Research Centre at Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK.
authors.forename: Frank O
authors.initials: FO
authors.lastname: Nestle
mesh_terms: D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007154:Immune System Diseases / Q000235:genetics*; D016130:Immunophenotyping; D007962:Leukocytes / Q000166:cytology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017452:Receptors, IgG / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000166:cytology
chemical_list: D017452:Receptors, IgG