Single-cell eQTL mapping identifies cell type–specific genetic control of autoimmune disease

Author:

Yazar Seyhan1ORCID,Alquicira-Hernandez Jose12ORCID,Wing Kristof34ORCID,Senabouth Anne1,Gordon M. Grace567ORCID,Andersen Stacey2,Lu Qinyi3ORCID,Rowson Antonia38,Taylor Thomas R. P.3ORCID,Clarke Linda9,Maccora Katia38,Chen Christine8,Cook Anthony L.10ORCID,Ye Chun Jimmie5671112ORCID,Fairfax Kirsten A.3,Hewitt Alex W.349ORCID,Powell Joseph E.113ORCID

Affiliation:

1. Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, NSW, Australia.

2. Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.

3. Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.

4. Department of Ophthalmology, Royal Hobart Hospital, Hobart, TAS, Australia.

5. Division of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

6. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.

7. Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.

8. Department of Surgery, School of Clinical Science at Monash Health, Monash University, VIC, Australia.

9. Centre for Eye Research Australia, University of Melbourne, East Melbourne, VIC, Australia.

10. Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, TAS, Australia.

11. Institute of Computational Health Sciences, University of California, San Francisco, San Francisco, CA, USA.

12. Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.

13. UNSW Cellular Genomics Futures Institute, University of New South Wales, Sydney, NSW, Australia.

Abstract

The human immune system displays substantial variation between individuals, leading to differences in susceptibility to autoimmune disease. We present single-cell RNA sequencing (scRNA-seq) data from 1,267,758 peripheral blood mononuclear cells from 982 healthy human subjects. For 14 cell types, we identified 26,597 independent cis-expression quantitative trait loci (eQTLs) and 990 trans-eQTLs, with most showing cell type–specific effects on gene expression. We subsequently show how eQTLs have dynamic allelic effects in B cells that are transitioning from naïve to memory states and demonstrate how commonly segregating alleles lead to interindividual variation in immune function. Finally, using a Mendelian randomization approach, we identify the causal route by which 305 risk loci contribute to autoimmune disease at the cellular level. This work brings together genetic epidemiology with scRNA-seq to uncover drivers of interindividual variation in the immune system.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3