近日，英国威康桑格研究所Nicole Soranzo等研究人员合作揭示血液性状和疾病的多基因和单基因基础。相关论文于2020年9月3日发表于《细胞》。
Title: The Polygenic and Monogenic Basis of Blood Traits and Diseases
Author: Dragana Vuckovic, Erik L. Bao, Parsa Akbari, Caleb A. Lareau, Abdou Mousas, Tao Jiang, Ming-Huei Chen, Laura M. Raffield, Manuel Tardaguila, Jennifer E. Huffman, Scott C. Ritchie, Karyn Megy, Hannes Ponstingl, Christopher J. Penkett, Patrick K. Albers, Emilie M. Wigdor, Saori Sakaue, Arden Moscati, Regina Manansala, Ken Sin Lo, Huijun Qian, Masato Akiyama, Traci M. Bartz, Yoav Ben-Shlomo, Andrew Beswick, Jette Bork-Jensen, Erwin P. Bottinger, Jennifer A. Brody, Frank J.A. van Rooij, Kumaraswamy N. Chitrala, Peter W.F. Wilson, Hélène Choquet, John Danesh, Emanuele Di Angelantonio, Niki Dimou, Jingzhong Ding, Paul Elliott, Tnu Esko, Michele K. Evans, Stephan B. Felix, James S. Floyd, Linda Broer, Niels Grarup, Michael H. Guo, Qi Guo, Andreas Greinacher, Jeff Haessler, Torben Hansen, Joanna M.M. Howson
Issue&Volume: 2020/09/03
Abstract: Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation.
DOI: 10.1016/j.cell.2020.08.008
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30999-5