Loth Daan W, Soler Artigas María, Gharib Sina A, Wain Louise V, Franceschini Nora, Koch Beate, Pottinger Tess D, Smith Albert Vernon, Duan Qing, Oldmeadow Chris, Lee Mi Kyeong, Strachan David P, James Alan L, Huffman Jennifer E, Vitart Veronique, Ramasamy Adaikalavan, Wareham Nicholas J, Kaprio Jaakko, Wang Xin-Qun, Trochet Holly, Kähönen Mika, Flexeder Claudia, Albrecht Eva, Lopez Lorna M, de Jong Kim, Thyagarajan Bharat, Alves Alexessander Couto, Enroth Stefan, Omenaas Ernst, Joshi Peter K, Fall Tove, Viñuela Ana, Launer Lenore J, Loehr Laura R, Fornage Myriam, Li Guo, Wilk Jemma B, Tang Wenbo, Manichaikul Ani, Lahousse Lies, Harris Tamara B, North Kari E, Rudnicka Alicja R, Hui Jennie, Gu Xiangjun, Lumley Thomas, Wright Alan F, Hastie Nicholas D, Campbell Susan, Kumar Rajesh, Pin Isabelle, Scott Robert A, Pietiläinen Kirsi H, Surakka Ida, Liu Yongmei, Holliday Elizabeth G, Schulz Holger, Heinrich Joachim, Davies Gail, Vonk Judith M, Wojczynski Mary, Pouta Anneli, Johansson Asa, Wild Sarah H, Ingelsson Erik, Rivadeneira Fernando, Völzke Henry, Hysi Pirro G, Eiriksdottir Gudny, Morrison Alanna C, Rotter Jerome I, Gao Wei, Postma Dirkje S, White Wendy B, Rich Stephen S, Hofman Albert, Aspelund Thor, Couper David, Smith Lewis J, Psaty Bruce M, Lohman Kurt, Burchard Esteban G, Uitterlinden André G, Garcia Melissa, Joubert Bonnie R, McArdle Wendy L, Musk A Bill, Hansel Nadia, Heckbert Susan R, Zgaga Lina, van Meurs Joyce B J, Navarro Pau, Rudan Igor, Oh Yeon-Mok, Redline Susan, Jarvis Deborah L, Zhao Jing Hua, Rantanen Taina, O'Connor George T, Ripatti Samuli, Scott Rodney J, Karrasch Stefan, Grallert Harald, Gaddis Nathan C, Starr John M, Wijmenga Cisca, Minster Ryan L, Lederer David J, Pekkanen Juha, Gyllensten Ulf, Campbell Harry, Morris Andrew P, Gläser Sven, Hammond Christopher J, Burkart Kristin M, Beilby John, Kritchevsky Stephen B, Gudnason Vilmundur, Hancock Dana B, Williams O Dale, Polasek Ozren, Zemunik Tatijana, Kolcic Ivana, Petrini Marcy F, Wjst Matthias, Kim Woo Jin, Porteous David J, Scotland Generation, Smith Blair H, Viljanen Anne, Heliövaara Markku, Attia John R, Sayers Ian, Hampel Regina, Gieger Christian, Deary Ian J, Boezen H Marike, Newman Anne, Jarvelin Marjo-Riitta, Wilson James F, Lind Lars, Stricker Bruno H, Teumer Alexander, Spector Timothy D, Melén Erik, Peters Marjolein J, Lange Leslie A, Barr R Graham, Bracke Ken R, Verhamme Fien M, Sung Joohon, Hiemstra Pieter S, Cassano Patricia A, Sood Akshay, Hayward Caroline, Dupuis Josée, Hall Ian P, Brusselle Guy G, Tobin Martin D, London Stephanie J
1] Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands. [2] Netherlands Health Care Inspectorate, The Hague, the Netherlands. [3].
1] Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, UK. [2] National Institute for Health Research (NIHR) Leicester Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester, UK. [3].
Nat Genet. 2014 Jul;46(7):669-77. doi: 10.1038/ng.3011. Epub 2014 Jun 15.
Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
用力肺活量（FVC）是一种通过肺量计测量的肺功能指标，反映肺容积，用于诊断和监测肺部疾病。我们对来自26项研究的52253名个体的FVC进行了全基因组关联研究荟萃分析，并在另外32917名欧洲血统个体中对顶级关联进行了随访。我们发现了六个在全基因组水平上具有显著意义（P < 5 × 10⁻⁸）的与FVC相关的新区域，分别位于EFEMP1、BMP6、MIR129 - 2 - HSD17B12、PRDM11、WWOX和KCNJ2基因内或其附近。两个先前与肺量计测量指标相关的基因座（GSTCD和PTCH1）也与FVC有关。我们在非裔美国人、韩国人、中国人和西班牙裔个体的样本中对新发现的区域进行了随访。我们在人类肺组织中检测到了所有六个新发现基因的转录本。这些新基因座可能为肺发育和限制性肺病发病机制提供线索。
