title: No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis.
abstract: In recent years, genome-wide association studies have identified 58 independent risk loci for coronary artery disease (CAD) on the autosome. However, due to the sex-specific data structure of the X chromosome, it has been excluded from most of these analyses. While females have 2 copies of chromosome X, males have only one. Also, one of the female X chromosomes may be inactivated. Therefore, special test statistics and quality control procedures are required. Thus, little is known about the role of X-chromosomal variants in CAD. To fill this gap, we conducted a comprehensive X-chromosome-wide meta-analysis including more than 43,000 CAD cases and 58,000 controls from 35 international study cohorts. For quality control, sex-specific filters were used to adequately take the special structure of X-chromosomal data into account. For single study analyses, several logistic regression models were calculated allowing for inactivation of one female X-chromosome, adjusting for sex and investigating interactions between sex and genetic variants. Then, meta-analyses including all 35 studies were conducted using random effects models. None of the investigated models revealed genome-wide significant associations for any variant. Although we analyzed the largest-to-date sample, currently available methods were not able to detect any associations of X-chromosomal variants with CAD.
authors.affiliation: Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.|DZHK (German Centre for Cardiovascular Research), partner site Hamburg-Lübeck-Kiel, Lübeck, Germany.
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authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.|NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
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authors.affiliation: DZHK (German Centre for Cardiovascular Research), partner site Hamburg-Lübeck-Kiel, Lübeck, Germany.|Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany and University Heart Center Luebeck, Campus Lübeck, Lübeck, Germany.
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authors.affiliation: The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, USA.|The Center for Statistical Genetics, Icahn School of Medicine at Mount Sinai, New York, USA.|The Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, USA.|The Zena and Michael A. Weiner Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, USA.
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authors.affiliation: The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, USA.|The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, USA.
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authors.affiliation: Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.|Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.|Oklahoma Center for Neuroscience, Oklahoma City, Oklahoma, USA.
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authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.|Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.|Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia.
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authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.|Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.|Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.|Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
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authors.affiliation: DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, München, Germany.|Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
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authors.initials: H
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authors.affiliation: DZHK (German Centre for Cardiovascular Research), partner site Hamburg-Lübeck-Kiel, Lübeck, Germany.|Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany and University Heart Center Luebeck, Campus Lübeck, Lübeck, Germany.
authors.forename: Jeanette
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authors.affiliation: Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.|DZHK (German Centre for Cardiovascular Research), partner site Hamburg-Lübeck-Kiel, Lübeck, Germany.
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mesh_terms: D041321:Chromosomes, Human, X; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D006801:Humans; D038622:Internationality; D008297:Male