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

Astle, WJ; Elding, H; Jiang, T; Allen, D; Ruklisa, D; Mann, AL; Mead, D; ... Soranzo, N; + view all (2016) The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease. Cell , 167 (5) pp. 1415-1429. 10.1016/j.cell.2016.10.042. Green open access

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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.

Type: Article
Title: The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cell.2016.10.042
Publisher version: http://dx.doi.org/10.1016/j.cell.2016.10.042
Language: English
Additional information: © 2017 The Authors. Published by Elsevier Inc. This is an open access article under the Creative Commons Attribution 4.0 International (CC BY 4.0) license (http://creativecommons.org/licenses/by/4.0/)
Keywords: Genome-wide Association, Coronary-artery-disease, Mendelian Randomization, Platelet Disorders, Genetic-variation, Identifies Loci, Whole-exome, Variants, Risk, Phenotype
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/1530707
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