Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.

Study design showing cohorts used in each stage of the analysis. ARIC = Atherosclerosis Risk in Communities Study, B58 = British 1958 Birth Cohort, CHS = Cardiovascular Health Study, COPACETIC = COPD Pathology: Addressing Critical gaps, Early Treatment & Diagnosis and Innovative Concepts, ECLIPSE = Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points, eQTL = Lung Expression Quantitative Trait Loci Study, FHS = Framingham Heart Study, KARE = Korean Association Resource project, MESA = Multi-Ethnic Study of Atherosclerosis, NETT-NAS = National Emphysema Treatment Trial/Normative Aging Study, RS = Rotterdam Study, SPIROMICS = Subpopulations and intermediate outcome measures in COPD study, EOCOPD = Boston Early-Onset COPD Study, ICGN = International COPD Genetics Network, TCGS = Transcontinental COPD Genetics Study, UK BiLEVE = UK Biobank Lung Exome Variant Evaluation; NHW = Non-Hispanic white, AA = African American, EA = European American. * Studies without genome-wide array genotyping (custom genotyping)

Manhattan plot showing P values for Stage 1 analysis (small open diamonds) with overlay of overall meta-analysis P values for SNPs analyzed in UK BiLEVE Stage 2 analysis (filled circles). Gene names in gray are previously described COPD or lung function (FEV1 or FEV1/FVC) loci; black are novel loci discovered in this study. The Stage 1 cohorts with available genotyping data (Supplementary Figures 1a–v) and the UK BiLEVE cohort determined the sample size for each top variant. The red dashed line indicates the threshold for genome-wide significance (P value < 5×10−8).

a–d Regional association for novel lociLocusZoom plots showing regional association of variants at the four novel COPD loci. The point size is proportional to the sample size, where Stage 1 cohorts with available genotyping data (Supplementary Figures 1a–v) and the UK BiLEVE cohort determined the sample size for each top variant.

Genetic correlation (using LD score regression) between COPD and other traitsShading and numbers represents strength of correlation. An asterisk indicates nominal (P < 0.05) significance, and a double asterisk indicates significant after Bonferroni correction for number of pairwise comparisons. fev1fvc and fev1 = lung function (FEV1/FVC ratio and FEV1 from CHARGE/SpiroMeta4, asthma taken from the asthma GWAS by the GABRIEL Consortium43, ild = pulmonary fibrosis from Fingerlin et al.8,9, bilSmk = subset of smokers in the UK BiLEVE study7, smkCpd = cigarettes per day smoking from the Tobacco and Genetics (TAG) Consortium45, smkFormer = current versus former smokers from TAG, smkOnset = age of smoking initiation from TAG, smkEver = ever versus never smoking from TAG. cad = coronary artery disease from the CARDIoGRAM study50, height51 and bmi (body mass index)52 from the GIANT consortium, bmdLumbar and bmdFemoral = lumbar and femoral bone mineral density, respectively, from the Genetic Factors for Osteoporosis (GeFOS) Consortium53.