TY - JOUR
T1 - Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function
AU - Hancock, Dana B.
AU - Eijgelsheim, Mark
AU - Wilk, Jemma B.
AU - Gharib, Sina A.
AU - Loehr, Laura R.
AU - Marciante, Kristin D.
AU - Franceschini, Nora
AU - Van Durme, Yannick M.T.A.
AU - Chen, Ting Hsu
AU - Barr, R. Graham
AU - Schabath, Matthew B.
AU - Couper, David J.
AU - Brusselle, Guy G.
AU - Psaty, Bruce M.
AU - Van Duijn, Cornelia M.
AU - Rotter, Jerome I.
AU - Uitterlinden, André G.
AU - Hofman, Albert
AU - Punjabi, Naresh M.
AU - Rivadeneira, Fernando
AU - Morrison, Alanna C.
AU - Enright, Paul L.
AU - North, Kari E.
AU - Heckbert, Susan R.
AU - Lumley, Thomas
AU - Stricker, Bruno H.C.
AU - O'Connor, George T.
AU - London, Stephanie J.
N1 - Funding Information:
The CHS research reported in this article was supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, grant numbers U01 HL080295 and R01 HL087652 from the US NIH National Heart, Lung, and Blood Institute, with additional contribution from the US NIH National Institute of Neurological Disorders and Stroke. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping was supported in part by US NIH National Center for Research Resources grant M01-RR00425 to the Cedars-Sinai General Clinical Research Center Genotyping core and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center. Research was conducted in part using data and resources from the FHS of the National Heart, Lung, and Blood Institute of the US NIH and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the FHS investigators participating in the SNP Health Association Resource (SHARe) project. This work was partially supported by the US NIH National Heart, Lung, and Blood Institute’s FHS (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc. for genotyping services (Contract No. N02-HL-6-4278). A portion of this research used the Linux Cluster for Genetic Analysis (LinGA-II), which is funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. J.B.W. is supported by a Young Clinical Scientist Award from the Flight Attendant Medical Research Institute (FAMRI). The Rotterdam Study was supported from grants from the Netherlands Organisation of Scientific Research (NOW) Investments (175.010.2005.011, 911-03-012); the Research Institute for Diseases in the Elderly (014-93-015; RIDE2); the Netherlands Genomics Initiative (NGI)/NWO (050-060-810); Erasmus Medical Center, Erasmus University, Rotterdam, The Netherlands; Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Ministry of Education, Culture and Science; the Ministry for Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. The authors thank P. Arp, M. Jhamai, M. Moorhouse, M. Verkerk, and S. Bervoets for their help in creating the Rotterdam GWAS database; T. A. Knoch, L. V. de Zeeuw, A. Abuseiris and R. de Graaf as well as their institutions, the Erasmus Computing Grid, Rotterdam, The Netherlands, and the national German MediGRID and Services@MediGRID part of the German D-Grid (German Bundesministerium fur Forschung und Technology) (#01 AK 803 A-H and # 01 IG 07015 G) for access to grid resources.
Funding Information:
This work was supported in part by the Intramural Research Program of the US National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Department of Health and Human Services (Z01ES043012). The ARIC study is carried out as a collaborative study supported by US NIH National Heart, Lung,
PY - 2010/1
Y1 - 2010/1
N2 - Spirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV 1) and its ratio to forced vital capacity (FEV1 /FVC), an indicator of airflow obstruction. This meta-analysis included 20,890 participants of European ancestry from four CHARGE Consortium studies: Atherosclerosis Risk in Communities, Cardiovascular Health Study, Framingham Heart Study and Rotterdam Study. We identified eight loci associated with FEV 1 /FVC (HHIP, GPR126, ADAM19, AGER-PPT2, FAM13A, PTCH1, PID1 and HTR4) and one locus associated with FEV 1 (INTS12-GSTCD-NPNT) at or near genome-wide significance (P 5 × 10-8) in the CHARGE Consortium dataset. Our findings may offer insights into pulmonary function and pathogenesis of chronic lung disease.
AB - Spirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV 1) and its ratio to forced vital capacity (FEV1 /FVC), an indicator of airflow obstruction. This meta-analysis included 20,890 participants of European ancestry from four CHARGE Consortium studies: Atherosclerosis Risk in Communities, Cardiovascular Health Study, Framingham Heart Study and Rotterdam Study. We identified eight loci associated with FEV 1 /FVC (HHIP, GPR126, ADAM19, AGER-PPT2, FAM13A, PTCH1, PID1 and HTR4) and one locus associated with FEV 1 (INTS12-GSTCD-NPNT) at or near genome-wide significance (P 5 × 10-8) in the CHARGE Consortium dataset. Our findings may offer insights into pulmonary function and pathogenesis of chronic lung disease.
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U2 - 10.1038/ng.500
DO - 10.1038/ng.500
M3 - Article
C2 - 20010835
AN - SCOPUS:73349111257
VL - 42
SP - 45
EP - 52
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 1
ER -