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

Research output: Contribution to journalArticlepeer-review

217 Citations (Scopus)
295 Downloads (Pure)


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 languageEnglish
Pages (from-to)387-403
Number of pages17
Issue number2
Early online date12 Mar 2015
Publication statusPublished - 9 Apr 2015


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