title: Common genetic determinants of lung function, subclinical atherosclerosis and risk of coronary artery disease.
abstract: Chronic obstructive pulmonary disease (COPD) independently associates with an increased risk of coronary artery disease (CAD), but it has not been fully investigated whether this co-morbidity involves shared pathophysiological mechanisms. To identify potential common pathways across the two diseases, we tested all recently published single nucleotide polymorphisms (SNPs) associated with human lung function (spirometry) for association with carotid intima-media thickness (cIMT) in 3,378 subjects with multiple CAD risk factors, and for association with CAD in a case-control study of 5,775 CAD cases and 7,265 controls. SNPs rs2865531, located in the CFDP1 gene, and rs9978142, located in the KCNE2 gene, were significantly associated with CAD. In addition, SNP rs9978142 and SNP rs3995090 located in the HTR4 gene, were associated with average and maximal cIMT measures. Genetic risk scores combining the most robustly spirometry-associated SNPs from the literature were modestly associated with CAD, (odds ratio (OR) (95% confidence interval (CI95) = 1.06 (1.03, 1.09); P-value = 1.5 × 10(-4), per allele). In conclusion, our study suggests that some genetic loci implicated in determining human lung function also influence cIMT and susceptibility to CAD. The present results should help elucidate the molecular underpinnings of the co-morbidity observed across COPD and CAD.
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Sabater-Lleal
authors.affiliation: Pfizer Worldwide Research and Development, Cambridge, United Kingdom.
authors.forename: Anders
authors.initials: A
authors.lastname: Mälarstig
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Lasse
authors.initials: L
authors.lastname: Folkersen
authors.affiliation: Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, United Kingdom; National Institute for Health Research, Leicester Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: María
authors.initials: M
authors.lastname: Soler Artigas
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan, Italy; Centro Cardiologico Monzino, Istituto di Ricovero e Cura a Cattere Scientifico, Milan, Italy.
authors.forename: Damiano
authors.initials: D
authors.lastname: Baldassarre
authors.affiliation: Department of Epidemiology, Erasmus Medical Center - University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Maryam
authors.initials: M
authors.lastname: Kavousi
authors.affiliation: Department of Clinical Sciences, Lunds University, Malmö, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Almgren
authors.affiliation: Centro Cardiologico Monzino, Istituto di Ricovero e Cura a Cattere Scientifico, Milan, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Veglia
authors.affiliation: Department of Epidemiology, Erasmus Medical Center - University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Internal Medicine, Erasmus Medical Center - University Medical Center Rotterdam, Rotterdam, the Netherlands; Inspectorate for Health Care, The Hague, the Netherlands.
authors.forename: Guy
authors.initials: G
authors.lastname: Brusselle
authors.affiliation: Department of Epidemiology, Erasmus Medical Center - University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Clinical Sciences, Lunds University, Malmö, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Engström
authors.affiliation: Department of Epidemiology, Erasmus Medical Center - University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
authors.affiliation: Department of Clinical Sciences, Lunds University, Malmö, Sweden; Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
authors.affiliation: Cardiovascular Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Paulsson-Berne
authors.affiliation: Department of Cardiovascular Medicine and the Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Hugh
authors.initials: H
authors.lastname: Watkins
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Eriksson
authors.affiliation: Center for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, United Kingdom.
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan, Italy; Centro Cardiologico Monzino, Istituto di Ricovero e Cura a Cattere Scientifico, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Tremoli
authors.affiliation: Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: de Faire
authors.affiliation: Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester, United Kingdom; National Institute for Health Research, Leicester Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Tobin
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Hamsten
mesh_terms: D050197:Atherosclerosis / Q000235:genetics*; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D008168:Lung / Q000502:physiology*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012123:Pulmonary Ventilation / Q000235:genetics*; D012306:Risk; D013147:Spirometry
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