The Polygenic and Monogenic Basis of Blood Traits and Diseases.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Vuckovic, D; Bao, EL; Akbari, P; Lareau, CA; Mousas, A; Jiang, T; Chen, M-H; Raffield, LM; Tardaguila, M; Huffman, JE; Ritchie, SC; Megy, K; Ponstingl, H; Penkett, CJ; Albers, PK; Wigdor, EM; Sakaue, S; Moscati, A; Manansala, R; Lo, KS; Qian, H; Akiyama, M; Bartz, TM; Ben-Shlomo, Y; Beswick, A; Bork-Jensen, J; Bottinger, EP; Brody, JA; van Rooij, FJA; Chitrala, KN; Wilson, PWF; Choquet, H; Danesh, J; Di Angelantonio, E; Dimou, N; Ding, J; Elliott, P; Esko, T; Evans, MK; Felix, SB; Floyd, JS; Broer, L; Grarup, N; Guo, MH; Guo, Q; Greinacher, A; Haessler, J; Hansen, T; Howson, JMM; Huang, W; Jorgenson, E; Kacprowski, T; Kähönen, M; Kamatani, Y; Kanai, M; Karthikeyan, S; Koskeridis, F; Lange, LA; Lehtimäki, T; Linneberg, A; Liu, Y; Lyytikäinen, L-P; Manichaikul, A; Matsuda, K; Mohlke, KL; Mononen, N; Murakami, Y; Nadkarni, GN; Nikus, K; Pankratz, N; Pedersen, O; Preuss, M; Psaty, BM; Raitakari, OT; Rich, SS; Rodriguez, BAT; Rosen, JD; Rotter, JI; Schubert, P; Spracklen, CN; Surendran, P; Tang, H; Tardif, J-C; Ghanbari, M; Völker, U; Völzke, H; Watkins, NA; Weiss, S; VA Million Veteran Program, ; Cai, N; Kundu, K; Watt, SB; Walter, K; Zonderman, AB; Cho, K; Li, Y; Loos, RJF; Knight, JC; Georges, M; Stegle, O; Evangelou, E; Okada, Y; Roberts, DJ; Inouye, M; Johnson, AD; Auer, PL; Astle, WJ; Reiner, AP; Butterworth, AS; Ouwehand, WH; Lettre, G; Sankaran, VG; Soranzo, N

Published Date

  • September 3, 2020

Published In

Volume / Issue

  • 182 / 5

Start / End Page

  • 1214 - 1231.e11

PubMed ID

  • 32888494

Pubmed Central ID

  • PMC7482360

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2020.08.008

Language

  • eng

Conference Location

  • United States