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The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease
Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell,...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300907/ https://www.ncbi.nlm.nih.gov/pubmed/27863252 http://dx.doi.org/10.1016/j.cell.2016.10.042 |
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author | Astle, William J. Elding, Heather Jiang, Tao Allen, Dave Ruklisa, Dace Mann, Alice L. Mead, Daniel Bouman, Heleen Riveros-Mckay, Fernando Kostadima, Myrto A. Lambourne, John J. Sivapalaratnam, Suthesh Downes, Kate Kundu, Kousik Bomba, Lorenzo Berentsen, Kim Bradley, John R. Daugherty, Louise C. Delaneau, Olivier Freson, Kathleen Garner, Stephen F. Grassi, Luigi Guerrero, Jose Haimel, Matthias Janssen-Megens, Eva M. Kaan, Anita Kamat, Mihir Kim, Bowon Mandoli, Amit Marchini, Jonathan Martens, Joost H.A. Meacham, Stuart Megy, Karyn O’Connell, Jared Petersen, Romina Sharifi, Nilofar Sheard, Simon M. Staley, James R. Tuna, Salih van der Ent, Martijn Walter, Klaudia Wang, Shuang-Yin Wheeler, Eleanor Wilder, Steven P. Iotchkova, Valentina Moore, Carmel Sambrook, Jennifer Stunnenberg, Hendrik G. Di Angelantonio, Emanuele Kaptoge, Stephen Kuijpers, Taco W. Carrillo-de-Santa-Pau, Enrique Juan, David Rico, Daniel Valencia, Alfonso Chen, Lu Ge, Bing Vasquez, Louella Kwan, Tony Garrido-Martín, Diego Watt, Stephen Yang, Ying Guigo, Roderic Beck, Stephan Paul, Dirk S. Pastinen, Tomi Bujold, David Bourque, Guillaume Frontini, Mattia Danesh, John Roberts, David J. Ouwehand, Willem H. Butterworth, Adam S. Soranzo, Nicole |
author_facet | Astle, William J. Elding, Heather Jiang, Tao Allen, Dave Ruklisa, Dace Mann, Alice L. Mead, Daniel Bouman, Heleen Riveros-Mckay, Fernando Kostadima, Myrto A. Lambourne, John J. Sivapalaratnam, Suthesh Downes, Kate Kundu, Kousik Bomba, Lorenzo Berentsen, Kim Bradley, John R. Daugherty, Louise C. Delaneau, Olivier Freson, Kathleen Garner, Stephen F. Grassi, Luigi Guerrero, Jose Haimel, Matthias Janssen-Megens, Eva M. Kaan, Anita Kamat, Mihir Kim, Bowon Mandoli, Amit Marchini, Jonathan Martens, Joost H.A. Meacham, Stuart Megy, Karyn O’Connell, Jared Petersen, Romina Sharifi, Nilofar Sheard, Simon M. Staley, James R. Tuna, Salih van der Ent, Martijn Walter, Klaudia Wang, Shuang-Yin Wheeler, Eleanor Wilder, Steven P. Iotchkova, Valentina Moore, Carmel Sambrook, Jennifer Stunnenberg, Hendrik G. Di Angelantonio, Emanuele Kaptoge, Stephen Kuijpers, Taco W. Carrillo-de-Santa-Pau, Enrique Juan, David Rico, Daniel Valencia, Alfonso Chen, Lu Ge, Bing Vasquez, Louella Kwan, Tony Garrido-Martín, Diego Watt, Stephen Yang, Ying Guigo, Roderic Beck, Stephan Paul, Dirk S. Pastinen, Tomi Bujold, David Bourque, Guillaume Frontini, Mattia Danesh, John Roberts, David J. Ouwehand, Willem H. Butterworth, Adam S. Soranzo, Nicole |
author_sort | Astle, William J. |
collection | PubMed |
description | Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal. |
format | Online Article Text |
id | pubmed-5300907 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-53009072017-02-17 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease Astle, William J. Elding, Heather Jiang, Tao Allen, Dave Ruklisa, Dace Mann, Alice L. Mead, Daniel Bouman, Heleen Riveros-Mckay, Fernando Kostadima, Myrto A. Lambourne, John J. Sivapalaratnam, Suthesh Downes, Kate Kundu, Kousik Bomba, Lorenzo Berentsen, Kim Bradley, John R. Daugherty, Louise C. Delaneau, Olivier Freson, Kathleen Garner, Stephen F. Grassi, Luigi Guerrero, Jose Haimel, Matthias Janssen-Megens, Eva M. Kaan, Anita Kamat, Mihir Kim, Bowon Mandoli, Amit Marchini, Jonathan Martens, Joost H.A. Meacham, Stuart Megy, Karyn O’Connell, Jared Petersen, Romina Sharifi, Nilofar Sheard, Simon M. Staley, James R. Tuna, Salih van der Ent, Martijn Walter, Klaudia Wang, Shuang-Yin Wheeler, Eleanor Wilder, Steven P. Iotchkova, Valentina Moore, Carmel Sambrook, Jennifer Stunnenberg, Hendrik G. Di Angelantonio, Emanuele Kaptoge, Stephen Kuijpers, Taco W. Carrillo-de-Santa-Pau, Enrique Juan, David Rico, Daniel Valencia, Alfonso Chen, Lu Ge, Bing Vasquez, Louella Kwan, Tony Garrido-Martín, Diego Watt, Stephen Yang, Ying Guigo, Roderic Beck, Stephan Paul, Dirk S. Pastinen, Tomi Bujold, David Bourque, Guillaume Frontini, Mattia Danesh, John Roberts, David J. Ouwehand, Willem H. Butterworth, Adam S. Soranzo, Nicole Cell Resource Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal. Cell Press 2016-11-17 /pmc/articles/PMC5300907/ /pubmed/27863252 http://dx.doi.org/10.1016/j.cell.2016.10.042 Text en © 2016 The Authors. Published by Elsevier Inc. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Resource Astle, William J. Elding, Heather Jiang, Tao Allen, Dave Ruklisa, Dace Mann, Alice L. Mead, Daniel Bouman, Heleen Riveros-Mckay, Fernando Kostadima, Myrto A. Lambourne, John J. Sivapalaratnam, Suthesh Downes, Kate Kundu, Kousik Bomba, Lorenzo Berentsen, Kim Bradley, John R. Daugherty, Louise C. Delaneau, Olivier Freson, Kathleen Garner, Stephen F. Grassi, Luigi Guerrero, Jose Haimel, Matthias Janssen-Megens, Eva M. Kaan, Anita Kamat, Mihir Kim, Bowon Mandoli, Amit Marchini, Jonathan Martens, Joost H.A. Meacham, Stuart Megy, Karyn O’Connell, Jared Petersen, Romina Sharifi, Nilofar Sheard, Simon M. Staley, James R. Tuna, Salih van der Ent, Martijn Walter, Klaudia Wang, Shuang-Yin Wheeler, Eleanor Wilder, Steven P. Iotchkova, Valentina Moore, Carmel Sambrook, Jennifer Stunnenberg, Hendrik G. Di Angelantonio, Emanuele Kaptoge, Stephen Kuijpers, Taco W. Carrillo-de-Santa-Pau, Enrique Juan, David Rico, Daniel Valencia, Alfonso Chen, Lu Ge, Bing Vasquez, Louella Kwan, Tony Garrido-Martín, Diego Watt, Stephen Yang, Ying Guigo, Roderic Beck, Stephan Paul, Dirk S. Pastinen, Tomi Bujold, David Bourque, Guillaume Frontini, Mattia Danesh, John Roberts, David J. Ouwehand, Willem H. Butterworth, Adam S. Soranzo, Nicole The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease |
title | The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease |
title_full | The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease |
title_fullStr | The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease |
title_full_unstemmed | The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease |
title_short | The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease |
title_sort | allelic landscape of human blood cell trait variation and links to common complex disease |
topic | Resource |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300907/ https://www.ncbi.nlm.nih.gov/pubmed/27863252 http://dx.doi.org/10.1016/j.cell.2016.10.042 |
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