Soranzo Nicole, Spector Tim D, Mangino Massimo, Kühnel Brigitte, Rendon Augusto, Teumer Alexander, Willenborg Christina, Wright Benjamin, Chen Li, Li Mingyao, Salo Perttu, Voight Benjamin F, Burns Philippa, Laskowski Roman A, Xue Yali, Menzel Stephan, Altshuler David, Bradley John R, Bumpstead Suzannah, Burnett Mary-Susan, Devaney Joseph, Döring Angela, Elosua Roberto, Epstein Stephen E, Erber Wendy, Falchi Mario, Garner Stephen F, Ghori Mohammed J R, Goodall Alison H, Gwilliam Rhian, Hakonarson Hakon H, Hall Alistair S, Hammond Naomi, Hengstenberg Christian, Illig Thomas, König Inke R, Knouff Christopher W, McPherson Ruth, Melander Olle, Mooser Vincent, Nauck Matthias, Nieminen Markku S, O'Donnell Christopher J, Peltonen Leena, Potter Simon C, Prokisch Holger, Rader Daniel J, Rice Catherine M, Roberts Robert, Salomaa Veikko, Sambrook Jennifer, Schreiber Stefan, Schunkert Heribert, Schwartz Stephen M, Serbanovic-Canic Jovana, Sinisalo Juha, Siscovick David S, Stark Klaus, Surakka Ida, Stephens Jonathan, Thompson John R, Völker Uwe, Völzke Henry, Watkins Nicholas A, Wells George A, Wichmann H-Erich, Van Heel David A, Tyler-Smith Chris, Thein Swee Lay, Kathiresan Sekar, Perola Markus, Reilly Muredach P, Stewart Alexandre F R, Erdmann Jeanette, Samani Nilesh J, Meisinger Christa, Greinacher Andreas, Deloukas Panos, Ouwehand Willem H, Gieger Christian
Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.
Nat Genet. 2009 Nov;41(11):1182-90. doi: 10.1038/ng.467. Epub 2009 Oct 11.
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.
血液中细胞的数量和体积会影响包括癌症、心血管疾病、代谢性疾病、感染性疾病和免疫性疾病在内的多种病症。我们在此研究八个临床相关血液学参数的基因变异，这些参数包括血红蛋白水平、红细胞和白细胞计数以及血小板计数和体积。我们在来自六项基于欧洲人群的研究的13943个样本中描述了22个基因座内与这些血液学参数可重复相关的常见变异，其中6个与红细胞参数相关，15个与血小板参数相关，1个与白细胞总数相关。我们进一步在9479例病例和10527例对照中鉴定出12q24处与冠状动脉疾病和心肌梗死相关的一个长程单倍型。我们表明，这种单倍型表现出广泛的疾病多效性，因为它包含1型糖尿病、高血压和乳糜泻的已知风险基因座，并且已通过特定于欧洲及地理上邻近人群的选择性清除而传播。
