Journal
NATURE GENETICS
Volume 41, Issue 11, Pages 1182-U38Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.467
Keywords
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Categories
Funding
- Wellcome Trust [UKBS-CC1]
- EU [HEALTH-F2-2008-ENGAGE, QLG2-CT-2002-01254, LSHM-CT-2006-037593]
- National Institute for Health Research of England (NIHR) (TwinsUK)
- Helmholtz Zentrum Munchen
- German Research Center for Environmental Health, Neuherberg, Germany
- German Federal Ministry of Education and Research (BMBF)
- German National Genome Research Network (NGFN)
- Munich Center of Health Sciences (MC Health) (KORA)
- Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]
- Ministry of Cultural Affairs, Social Ministry of the Federal State of Mecklenburg-West Pomerania
- Deutsche Forschungsgemeinschaft [SFB TR 19]
- Siemens Healthcare, Erlangen, Germany
- Federal State of Mecklenburg-West Pomerania (SHIP)
- NIHR, CBMRC, NHSBT, (CBR)
- Deutsche Forschungsgemeinschaft
- German Federal Ministry of Education and Research (BMBF) [NGFN-2]
- Leicester NIHR Biomedical Research Unit in Cardiovascular Disease
- EU-FP6 [LSHM-CT-2004-503485]
- Cardiovascular Institute (University of Pennsylvania)
- GlaxoSmithKline
- MedSTAR Research Institute (PennCATH/MedSTAR)
- US National Institutes of Health (NIH)
- National Heart, Lung, and Blood Institute (STAMPEED)
- National Center for Research Resource [U54 RR020278]
- Canadian Institutes of Health Research [MOP82810, NA6650, MOP77682]
- Canada Foundation for Innovation and Ontario Research Foundation [11966]
- Finnish Foundation for Cardiovascular Research, Sigrid Juselius Foundation (COROGENE)
- Juvenile Diabetes Research Foundation/Wellcome Trust [T1D]
- MRC [G0000111] Funding Source: UKRI
- Medical Research Council [G0000111] Funding Source: researchfish
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The number and volume of cells in the blood affect a wide range of disorders including cancer and cardiovascular, metabolic, infectious and immune conditions. We consider here the genetic variation in eight clinically relevant hematological parameters, including hemoglobin levels, red and white blood cell counts and platelet counts and volume. We describe common variants within 22 genetic loci reproducibly associated with these hematological parameters in 13,943 samples from six European population-based studies, including 6 associated with red blood cell parameters, 15 associated with platelet parameters and 1 associated with total white blood cell count. We further identified a long-range haplotype at 12q24 associated with coronary artery disease and myocardial infarction in 9,479 cases and 10,527 controls. We show that this haplotype demonstrates extensive disease pleiotropy, as it contains known risk loci for type 1 diabetes, hypertension and celiac disease and has been spread by a selective sweep specific to European and geographically nearby populations.
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