Genetic architecture of the acute and persistent immune cell response after radiation exposure

Li He; Chenhan Zhong; Hang Chang; Jamie L Inman; Susan E Celniker; Myrsini Ioakeim-Ioannidou; Kevin X Liu; Daphne Haas-Kogan; Shannon M MacDonald; David W Threadgill; Scott C Kogan; Jian-Hua Mao; Antoine M Snijders

doi:10.1016/j.xgen.2023.100422

Genetic architecture of the acute and persistent immune cell response after radiation exposure

Cell Genom. 2023 Oct 6;3(11):100422. doi: 10.1016/j.xgen.2023.100422. eCollection 2023 Nov 8.

Authors

Li He^{1

2}, Chenhan Zhong^{2

3}, Hang Chang^{2

4}, Jamie L Inman^{2

4}, Susan E Celniker^{2

5}, Myrsini Ioakeim-Ioannidou⁶, Kevin X Liu⁷, Daphne Haas-Kogan⁷, Shannon M MacDonald⁶, David W Threadgill^{8

9}, Scott C Kogan¹⁰, Jian-Hua Mao^{2

4

5}, Antoine M Snijders^{2

4

5}

Affiliations

¹ Department of Hematology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430079, China.
² Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
³ Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
⁴ Berkeley Biomedical Data Science Center, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
⁵ Comparative Biochemistry Program, University of California Berkeley, Berkeley, CA 94720, USA.
⁶ Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
⁷ Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
⁸ Texas A&M Institute for Genome Sciences and Society, Texas A&M University, College Station, TX 77843, USA.
⁹ Departments of Nutrition and Cell Biology and Genetics, Texas A&M University, College Station, TX 77843, USA.
¹⁰ Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.

Abstract

Hematologic toxicity is a common side effect of multimodal cancer therapy. Nearly all animal studies investigating the causes of radiotherapy-induced hematologic toxicity use inbred strains with limited genetic diversity and do not reflect the diverse responses observed in humans. We used the population-based Collaborative Cross (CC) mouse resource to investigate the genetic architecture of the acute and persistent immune response after radiation exposure by measuring 22 immune parameters in 1,720 CC mice representing 35 strains. We determined relative acute and persistent radiation resistance scores at the individual strain level considering contributions from all immune parameters. Genome-wide association analysis identified quantitative trait loci associated with baseline and radiation responses. A cross-species radiation resistance score predicted recurrence-free survival in medulloblastoma patients. We present a community resource of immune parameters and genome-wide association analyses before and after radiation exposure for future investigations of the contributions of host genetics on radiosensitivity.

Keywords: Collaborative Cross mice; complete blood count; genome-wide association study; hematologic toxicity; radiation exposure.

Grants and funding

R21 AI145390/AI/NIAID NIH HHS/United States