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Cell. 2015 Apr 9;161(2):387-403. doi: 10.1016/j.cell.2015.02.046. Epub 2015 Mar 12.

The genetic architecture of the human immune system: a bioresource for autoimmunity and disease pathogenesis.

Author information

1
ImmunoTechnology Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA. Electronic address: roederer@nih.gov.
2
Department of Twin Research & Genetic Epidemiology, King's College London, London SE1 7EH, UK.
3
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.
4
ImmunoTechnology Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
5
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.
6
Cutaneous Medicine Unit, St. John's Institute of Dermatology, King's College London, London SE1 9RT, UK.
7
Department of Twin Research & Genetic Epidemiology, King's College London, London SE1 7EH, UK. Electronic address: tim.spector@kcl.ac.uk.

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.

PMID:
25772697
PMCID:
PMC4393780
DOI:
10.1016/j.cell.2015.02.046
[Indexed for MEDLINE]
Free PMC Article
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