Cited by 1,065Genetic Associations and EpidemiologyImmune responses and vaccinationsImmune Response and Inflammation

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Variation in the Human Immune System Is Largely Driven by Non-Heritable Influences

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Brodin, Petter, Jojic, Vladimir, Gao, Tianxiang, Bhattacharya, Sanchita, Angel, Cesar J. Lopez, Furman, David, Shen-Orr, Shai, Dekker, Cornelia L., Swan, Gary E., Butte, Atul J., Maecker, Holden T., Davis, Mark M.·2015·Cell

DOI 10.1016/j.cell.2014.12.020PMC PMC4302727

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Abstract

There is considerable heterogeneity in immunological parameters between individuals, but its sources are largely unknown. To assess the relative contribution of heritable versus non-heritable factors, we have performed a systems-level analysis of 210 healthy twins between 8 and 82 years of age. We measured 204 different parameters, including cell population frequencies, cytokine responses, and serum proteins, and found that 77% of these are dominated (>50% of variance) and 58% almost completely determined (>80% of variance) by non-heritable influences. In addition, some of these parameters become more variable with age, suggesting the cumulative influence of environmental exposure. Similarly, the serological responses to seasonal influenza vaccination are also determined largely by non-heritable factors, likely due to repeated exposure to different strains. Lastly, in MZ twins discordant for cytomegalovirus infection, more than half of all parameters are affected. These results highlight the largely reactive and adaptive nature of the immune system in healthy individuals.

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Self-citation
Circulating cytokines associated with clinical response to systemic therapy in metastatic renal cell carcinoma
Chehrazi‐Raffle, A., Meza, L. A., Alcantara, M. B., Dizman, N., Bergerot, P. G., Salgia, N., Hsu, J., Ruel, N. H., Salgia, S. K., Malhotra, J., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-002009 · Cited by 37

Authors: Brodin, P., Jojic, V., Gao, T., Bhattacharya, S., Angel, C. J. L., Furman, D., Shen-Orr, S., Dekker, C. L., Swan, G. E., Butte, A. J., Maecker, H. T., & Davis, M. M.
Affiliations: Science for Life Laboratory (SE)
University of North Carolina at Chapel Hill (US)
Stanford Medicine (US)
Technion – Israel Institute of Technology (IL)
Lucile Packard Children's Hospital (US)
Howard Hughes Medical Institute (US)
Corresponding author: Davis, Mark M.
ORCID: Brodin, Petter
Bhattacharya, Sanchita
Angel, Cesar J. Lopez
Furman, David
Shen-Orr, Shai
Dekker, Cornelia L.
Swan, Gary E.
Butte, Atul J.
Maecker, Holden T.
Davis, Mark M.
Venue: Cell
Publisher: Elsevier BV
Published: 2015-01
Volume: 160
Issue: 1-2
Pages: 37-47
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2014.12.020
PMC: PMC4302727
OpenAlex: W1978297432
Cited by: 1,065
References: 48
Citations by year: 2026: 67 · 2025: 82 · 2024: 93 · 2023: 84 · 2022: 85 · 2021: 115 · 2020: 106 · 2019: 102 · 2018: 109 · 2017: 96 · 2016: 80 · 2015: 45
FWCI: 75.61
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 379 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institutes of Health (UL1TR001085)
National Institute on Drug Abuse (R01DA011170, R01DA023063, DA011170, DA023063)
National Institute of Allergy and Infectious Diseases (AI090019, U19AI090019, U19AI057229)
National Institute of Environmental Health Sciences (R21ES022153, ES022153)
National Center for Research Resources (UL1RR025744)
National Center for Advancing Translational Sciences
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: monozygotic twins, cytokine response, serum proteins, environmental exposure, cytomegalovirus infection
MeSH terms: Adolescent, Adult, Aged, Aged, 80 and over, Blood Proteins, Child, Cytomegalovirus Infections, Humans, Immunity, Influenza Vaccines, Middle Aged, Twins, Dizygotic, Twins, Monozygotic, Cytokines, Young Adult

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Variation in the Human Immune System Is Largely Driven by Non-Heritable Influences

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