The Polygenic and Monogenic Basis of Blood Traits and Diseases

Research output: Contribution to journal › Journal article › Research › peer-review

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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.

In: Cell, Vol. 182, No. 5, 2020, p. 1214-1231.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

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, Hansen, T, Linneberg, A, Pedersen, O, Loos, RJF & VA Million Veteran Program 2020, 'The Polygenic and Monogenic Basis of Blood Traits and Diseases', Cell, vol. 182, no. 5, pp. 1214-1231. https://doi.org/10.1016/j.cell.2020.08.008

APA

Vuckovic, D., Bao, E. L., Akbari, P., Lareau, C. A., Mousas, A., Jiang, T., Chen, M-H., Raffield, L. M., Tardaguila, M., Huffman, J. E., Ritchie, S. C., Megy, K., Ponstingl, H., Penkett, C. J., Albers, P. K., Wigdor, E. M., Sakaue, S., Moscati, A., Manansala, R., ... VA Million Veteran Program (2020). The Polygenic and Monogenic Basis of Blood Traits and Diseases. Cell, 182(5), 1214-1231. https://doi.org/10.1016/j.cell.2020.08.008

Vancouver

Vuckovic D, Bao EL, Akbari P, Lareau CA, Mousas A, Jiang T et al. The Polygenic and Monogenic Basis of Blood Traits and Diseases. Cell. 2020;182(5):1214-1231. https://doi.org/10.1016/j.cell.2020.08.008

Author

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. / The Polygenic and Monogenic Basis of Blood Traits and Diseases. In: Cell. 2020 ; Vol. 182, No. 5. pp. 1214-1231.

Bibtex

@article{f80f28da8f5541719c47eecb948c8604,
title = "The Polygenic and Monogenic Basis of Blood Traits and Diseases",
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.",
keywords = "GENOME-WIDE ASSOCIATION, GENETIC ARCHITECTURE, CELL, VARIANTS, EFFICIENT, COMPLEX, COMMON, LOCI, RARE, INTERROGATION",
author = "Dragana Vuckovic and Bao, {Erik L.} and Parsa Akbari and Lareau, {Caleb A.} and Abdou Mousas and Tao Jiang and Ming-Huei Chen and Raffield, {Laura M.} and Manuel Tardaguila and Huffman, {Jennifer E.} and Ritchie, {Scott C.} and Karyn Megy and Hannes Ponstingl and Penkett, {Christopher J.} and Albers, {Patrick K.} and Wigdor, {Emilie M.} and Saori Sakaue and Arden Moscati and Regina Manansala and Lo, {Ken Sin} and Huijun Qian and Masato Akiyama and Bartz, {Traci M.} and Yoav Ben-Shlomo and Andrew Beswick and Jette Bork-Jensen and Bottinger, {Erwin P.} and Brody, {Jennifer A.} and {van Rooij}, {Frank J. A.} and Chitrala, {Kumaraswamy N.} and Wilson, {Peter W. F.} and Helene Choquet and John Danesh and {Di Angelantonio}, Emanuele and Niki Dimou and Jingzhong Ding and Paul Elliott and Tonu Esko and Evans, {Michele K.} and Felix, {Stephan B.} and Floyd, {James S.} and Linda Broer and Niels Grarup and Guo, {Michael H.} and Qi Guo and Andreas Greinacher and Torben Hansen and Allan Linneberg and Oluf Pedersen and Loos, {Ruth J. F.} and {VA Million Veteran Program}",
year = "2020",
doi = "10.1016/j.cell.2020.08.008",
language = "English",
volume = "182",
pages = "1214--1231",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",

}

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