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

Authors: Zhu, Zhaozhong; Wang, Xiaofang; Li, Xihao; Lin, Yifei; Shen, Sipeng; Liu, Cong-Lin; Hobbs, Brain D; Hasegawa, Kohei; Liang, Liming; International COPD Genetics Consortium; Boezen, H Marike; Camargo Jr, Carlos A; Cho, Michael H; Christiani, David C

Published In Respir Res, (2019 Apr 02)

Abstract: 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 (Ncase = 12,550, Ncontrol = 46,368) from the International COPD Genetics Consortium and four primary cardiac traits: resting heart rate (RHR) (N = 458,969), high blood pressure (HBP) (Ncase = 144,793, Ncontrol = 313,761), coronary artery disease (CAD)(Ncase = 60,801, Ncontrol = 123,504), and stroke (Ncase = 40,585, Ncontrol = 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.

PubMed ID: 30940143 Exiting the NIEHS site

MeSH Terms: Cardiovascular Diseases/diagnosis; Cardiovascular Diseases/epidemiology; Cardiovascular Diseases/genetics*; Databases, Genetic/trends; Genetic Predisposition to Disease/epidemiology; Genetic Predisposition to Disease/genetics; Genetic Variation/genetics*; Genome-Wide Association Study/methods*; Humans; Polymorphism, Single Nucleotide/genetics*; Pulmonary Disease, Chronic Obstructive/diagnosis; Pulmonary Disease, Chronic Obstructive/epidemiology; Pulmonary Disease, Chronic Obstructive/genetics*; Quantitative Trait, Heritable

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