Deep sequencing of 1320 genes reveals the landscape of protein-truncating variants and their contribution to psoriasis in 19,973 Chinese individuals

  1. Liangdan Sun1,3,4,5
  1. 1Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei 230032, China;
  2. 2School of Medicine, South China University of Technology, Guangzhou 510006, China;
  3. 3Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Anhui, Hefei 230032, China;
  4. 4Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei 230032, China;
  5. 5Anhui Provincial Institute of Translational Medicine, Hefei 230032, China;
  6. 6Guangdong Engineering Research Center of Life Sciences Bigdata, Shenzhen 518083, China;
  7. 7Department of Biology, University of Copenhagen, Copenhagen 2200, Denmark;
  8. 8Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA;
  9. 9Microsoft Corporation, Redmond, Washington 98052, USA;
  10. 10College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China;
  11. 11School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 510006, Guangdong, China;
  12. 12The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, China

  1. ↵13 These authors contributed equally to this work.

  • Corresponding authors: jakey{at}princeton.edu, jinxin{at}scut.edu.cn, sunld{at}ahmu.edu.cn

    • Abstract

    Protein-truncating variants (PTVs) have important impacts on phenotype diversity and disease. However, their population genetics characteristics in more globally diverse populations are not well defined. Here, we describe patterns of PTVs in 1320 genes sequenced in 10,539 healthy controls and 9434 patients with psoriasis, all of Han Chinese ancestry. We identify 8720 PTVs, of which 77% are novel, and estimate 88% of all PTVs are deleterious and subject to purifying selection. Furthermore, we show that individuals with psoriasis have a significantly higher burden of PTVs compared to controls (P = 0.02). Finally, we identified 18 PTVs in 14 genes with unusually high levels of population differentiation, consistent with the action of local adaptation. Our study provides insights into patterns and consequences of PTVs.

    Footnotes

    • Received June 27, 2020.
    • Accepted May 10, 2021.

    This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see https://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

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    1. Published in Advance June 21, 2021, doi: 10.1101/gr.267963.120 Genome Res. 31: 1150-1158 © 2021 Xu et al.; Published by Cold Spring Harbor Laboratory Press

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