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Background  A growing number of studies clearly demonstrate a substantial association between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVD), although little is known about the shared genetics that contribute to this association.    Methods  We conducted a large-scale cross-trait genome-wide association study to investigate genetic overlap between COPD (N case  = 12,550, N control  = 46,368) from the International COPD Genetics Consortium and four primary cardiac traits: resting heart rate (RHR) ( N  = 458,969), high blood pressure (HBP) (N case  = 144,793, N control  = 313,761), coronary artery disease (CAD)(N case  = 60,801, N control  = 123,504), and stroke (N case  = 40,585, N control  = 406,111) from UK Biobank, CARDIoGRAMplusC4D Consortium, and International Stroke Genetics Consortium data.    Results  RHR and HBP had modest genetic correlation, and CAD had borderline evidence with COPD at a genome-wide level. We found evidence of local genetic correlation with particular regions of the genome. Cross-trait meta-analysis of COPD identified 21 loci jointly associated with RHR, 22 loci with HBP, and 3 loci with CAD. Functional analysis revealed that shared genes were enriched in smoking-related pathways and in cardiovascular, nervous, and immune system tissues. An examination of smoking-related genetic variants identified SNPs located in 15q25.1 region associated with cigarettes per day, with effects on RHR and CAD. A Mendelian randomization analysis showed a significant positive causal effect of COPD on RHR (causal estimate = 0.1374,  P  = 0.008).    Conclusion  In a set of large-scale GWAS, we identify evidence of shared genetics between COPD and cardiac traits.    Electronic supplementary material  The online version of this article (10.1186/s12931-019-1036-8) contains supplementary material, which is available to authorized users.

Genetic overlap of chronic obstructive pulmonary disease and cardiovascular disease-related traits: a large-scale genome-wide cross-trait analysis