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

• Published in: Respiratory research Vol. 20; no. 1; pp. 64 - 14
• Main Authors: Zhu, Zhaozhong, Wang, Xiaofang, Li, Xihao, Lin, Yifei, Shen, Sipeng, Liu, Cong-Lin, Hobbs, Brain D, Hasegawa, Kohei, Liang, Liming, Boezen, H Marike, Camargo, Jr, Carlos A, Cho, Michael H, Christiani, David C
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 02.04.2019; BioMed Central; BMC
• Subjects: Air pollution; Annotations; Binding sites; Blood pressure; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - diagnosis; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - genetics; Chronic obstructive lung disease; Chronic obstructive pulmonary disease; Cigarettes; Consortia; Coronary artery; Coronary artery disease; Correlation analysis; Databases, Genetic - trends; Functional analysis; Gene expression; Gene loci; Genetic aspects; Genetic diversity; Genetic overlap; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; Genetic research; Genetic variance; Genetic Variation - genetics; Genetics; Genome-wide association studies; Genome-Wide Association Study - methods; Genomes; Genomics; Genotypes; Heart; Heart diseases; Heart rate; Humans; Hypertension; Identification and classification; Immune system; Lung diseases; Metabolism; Methods; Obstructive lung disease; Polymorphism, Single Nucleotide - genetics; Pulmonary Disease, Chronic Obstructive - diagnosis; Pulmonary Disease, Chronic Obstructive - epidemiology; Pulmonary Disease, Chronic Obstructive - genetics; Quantitative Trait, Heritable; Single-nucleotide polymorphism; Smoking; Stroke; Studies; United States; United Kingdom > UK; Cardiovascular diseases; Chronic obstructive pulmonary disease; Genetic overlap
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/s12931-019-1036-8

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. We conducted a large-scale cross-trait genome-wide association study to investigate genetic overlap between COPD (N  = 12,550, N  = 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  = 144,793, N  = 313,761), coronary artery disease (CAD)(N  = 60,801, N  = 123,504), and stroke (N  = 40,585, N  = 406,111) from UK Biobank, CARDIoGRAMplusC4D Consortium, and International Stroke Genetics Consortium data. 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). In a set of large-scale GWAS, we identify evidence of shared genetics between COPD and cardiac traits.