The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease

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• dc.contributor.author Astle, William J.ca
• dc.contributor.author Garrido Martín, Diego, 1992-ca
• dc.contributor.author Guigó Serra, Rodericca
• dc.contributor.author Soranzo, Nicoleca
• dc.date.accessioned 2017-03-29T10:46:37Z
• dc.date.available 2017-03-29T10:46:37Z
• dc.date.issued 2016
• dc.description.abstract 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.
• dc.format.mimetype application/pdfca
• dc.identifier.citation Astle WJ, Elding H, Jiang T, Allen D, Ruklisa D, Mann AL, Mead D, Bouman H, Riveros-Mckay F, Kostadima MA et al. The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease. Cell. 2016;167(5):1415-29. DOI: 10.1016/j.cell.2016.10.042
• dc.identifier.doi http://dx.doi.org/10.1016/j.cell.2016.10.042
• dc.identifier.issn 0092-8674
• dc.identifier.uri http://hdl.handle.net/10230/28320
• dc.language.iso eng
• dc.publisher Elsevierca
• dc.relation.ispartof Cell. 2016;167(5):1415-29
• dc.rights © Elsevier http://dx.doi.org/10.1016/j.cell.2016.10.042. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Blood
• dc.subject.keyword Genetics
• dc.subject.keyword Hematology
• dc.subject.keyword Epigenetics
• dc.subject.keyword Hematopoiesis
• dc.subject.keyword Mendelian randomization
• dc.subject.keyword Complex disease
• dc.subject.keyword Autoimmune diseases
• dc.subject.keyword Cardiovascular diseases
• dc.title The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Diseaseca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion