The Polygenic and Monogenic Basis of Blood Traits and Diseases
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
The Polygenic and Monogenic Basis of Blood Traits and Diseases. / Vuckovic, Dragana; Bao, Erik L.; Akbari, Parsa; Lareau, Caleb A.; Mousas, Abdou; Jiang, Tao; Chen, Ming-Huei; Raffield, Laura M.; Tardaguila, Manuel; Huffman, Jennifer E.; Ritchie, Scott C.; Megy, Karyn; Ponstingl, Hannes; Penkett, Christopher J.; Albers, Patrick K.; Wigdor, Emilie M.; Sakaue, Saori; Moscati, Arden; Manansala, Regina; Lo, Ken Sin; Qian, Huijun; Akiyama, Masato; Bartz, Traci M.; Ben-Shlomo, Yoav; Beswick, Andrew; Bork-Jensen, Jette; Bottinger, Erwin P.; Brody, Jennifer A.; van Rooij, Frank J. A.; Chitrala, Kumaraswamy N.; Wilson, Peter W. F.; Choquet, Helene; Danesh, John; Di Angelantonio, Emanuele; Dimou, Niki; Ding, Jingzhong; Elliott, Paul; Esko, Tonu; Evans, Michele K.; Felix, Stephan B.; Floyd, James S.; Broer, Linda; Grarup, Niels; Guo, Michael H.; Guo, Qi; Greinacher, Andreas; Hansen, Torben; Linneberg, Allan; Pedersen, Oluf; Loos, Ruth J. F.; VA Million Veteran Program.
I: Cell, Bind 182, Nr. 5, 2020, s. 1214-1231.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - The Polygenic and Monogenic Basis of Blood Traits and Diseases
AU - Vuckovic, Dragana
AU - Bao, Erik L.
AU - Akbari, Parsa
AU - Lareau, Caleb A.
AU - Mousas, Abdou
AU - Jiang, Tao
AU - Chen, Ming-Huei
AU - Raffield, Laura M.
AU - Tardaguila, Manuel
AU - Huffman, Jennifer E.
AU - Ritchie, Scott C.
AU - Megy, Karyn
AU - Ponstingl, Hannes
AU - Penkett, Christopher J.
AU - Albers, Patrick K.
AU - Wigdor, Emilie M.
AU - Sakaue, Saori
AU - Moscati, Arden
AU - Manansala, Regina
AU - Lo, Ken Sin
AU - Qian, Huijun
AU - Akiyama, Masato
AU - Bartz, Traci M.
AU - Ben-Shlomo, Yoav
AU - Beswick, Andrew
AU - Bork-Jensen, Jette
AU - Bottinger, Erwin P.
AU - Brody, Jennifer A.
AU - van Rooij, Frank J. A.
AU - Chitrala, Kumaraswamy N.
AU - Wilson, Peter W. F.
AU - Choquet, Helene
AU - Danesh, John
AU - Di Angelantonio, Emanuele
AU - Dimou, Niki
AU - Ding, Jingzhong
AU - Elliott, Paul
AU - Esko, Tonu
AU - Evans, Michele K.
AU - Felix, Stephan B.
AU - Floyd, James S.
AU - Broer, Linda
AU - Grarup, Niels
AU - Guo, Michael H.
AU - Guo, Qi
AU - Greinacher, Andreas
AU - Hansen, Torben
AU - Linneberg, Allan
AU - Pedersen, Oluf
AU - Loos, Ruth J. F.
AU - VA Million Veteran Program
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - GENOME-WIDE ASSOCIATION
KW - GENETIC ARCHITECTURE
KW - CELL
KW - VARIANTS
KW - EFFICIENT
KW - COMPLEX
KW - COMMON
KW - LOCI
KW - RARE
KW - INTERROGATION
U2 - 10.1016/j.cell.2020.08.008
DO - 10.1016/j.cell.2020.08.008
M3 - Journal article
C2 - 32888494
VL - 182
SP - 1214
EP - 1231
JO - Cell
JF - Cell
SN - 0092-8674
IS - 5
ER -
ID: 250117705