No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis

Christina Loley; Maris Alver; Themistocles L. Assimes; Andrew Bjonnes; Anuj Goel; Stefan Gustafsson; Jussi Hernesniemi; Jemma C. Hopewell; Stavroula Kanoni; Marcus E. Kleber; King Wai Lau; Yingchang Lu; Leo-Pekka Lyytikainen; Christopher P. Nelson; Majid Nikpay; Liming Qu; Elias Salfati; Markus Scholz; Taru Tukiainen; Christina Willenborg; Hong-Hee Won; Lingyao Zeng; Weihua Zhang; Sonia S. Anand; Frank Beutner; Erwin P. Bottinger; Robert Clarke; George Dedoussis; Ron Do; Tonu Esko; Markku Eskola; Martin Farrall; Dominique Gauguier; Vilmantas Giedraitis; Christopher B. Granger; Alistair S. Hall; Anders Hamsten; Stanley L. Hazen; Jie Huang; Mika Kahonen; Theodosios Kyriakou; Reijo Laaksonen; Lars Lind; Cecilia Lindgren; Patrik K. E. Magnusson; Eirini Marouli; Evelin Mihailov; Andrew P. Morris; Kjell Nikus; Nancy Pedersen; Loukianos Rallidis; Veikko Salomaa; Svati H. Shah; Alexandre F. R. Stewart; John R. Thompson; Pierre A. Zalloua; John C. Chambers; Rory Collins; Erik Ingelsson; Carlos Iribarren; Pekka J. Karhunen; Jaspal S. Kooner; Terho Lehtimaki; Ruth J. F. Loos; Winfried Maerz; Ruth McPherson; Andres Metspalu; Muredach P. Reilly; Samuli Ripatti; Dharambir K. Sanghera; Joachim Thiery; Hugh Watkins; Panos Deloukas; Sekar Kathiresan; Nilesh J. Samani; Heribert Schunkert; Jeanette Erdmann; Inke R. Koenig

doi:10.1038/srep35278

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No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis

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No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis

Christina Loley, Maris Alver, Themistocles L. Assimes, Andrew Bjonnes, Anuj Goel, Stefan Gustafsson, Jussi Hernesniemi, Jemma C. Hopewell, Stavroula Kanoni, Marcus E. Kleber, …

Scientific reports, Vol.6(1), pp.35278-35278

12/10/2016

DOI: https://doi.org/10.1038/srep35278

PMCID: PMC5059659

PMID: 27731410

Abstract

Multidisciplinary Sciences

Science & Technology

Science & Technology - Other Topics

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.

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Title: No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis
Creators - without role: Christina Loley - University of Lübeck
Maris Alver - University of Tartu
Themistocles L. Assimes - Stanford University
Andrew Bjonnes - Center for Human Genetics
Anuj Goel - University of Oxford
Stefan Gustafsson - Science for Life Laboratory
Jussi Hernesniemi - Fimlab
Jemma C. Hopewell - University of Oxford
Stavroula Kanoni - Queen Mary University of London
Marcus E. Kleber - Heidelberg University
King Wai Lau - University of Oxford
Yingchang Lu - Icahn School of Medicine at Mount Sinai
Leo-Pekka Lyytikainen - Fimlab
Christopher P. Nelson - University of Leicester
Majid Nikpay - Canadian Heart Research Centre
Liming Qu - University of Pennsylvania
Elias Salfati - Stanford University
Markus Scholz - Leipzig University
Taru Tukiainen - Massachusetts General Hospital
Christina Willenborg - German Centre for Cardiovascular Research
Hong-Hee Won - Samsung Medical Center
Lingyao Zeng - Deutsches Herzzentrum München
Weihua Zhang - Imperial College London
Sonia S. Anand - McMaster University
Frank Beutner - Leipzig Heart Institute
Erwin P. Bottinger - Icahn School of Medicine at Mount Sinai
Robert Clarke - University of Oxford
George Dedoussis - Harokopio University of Athens
Ron Do - Icahn School of Medicine at Mount Sinai
Tonu Esko - University of Tartu
Markku Eskola - Tampere University Hospital
Martin Farrall - University of Oxford
Dominique Gauguier - Centre de Recherche des Cordeliers
Vilmantas Giedraitis - Uppsala University
Christopher B. Granger - Duke University
Alistair S. Hall - University of Leeds
Anders Hamsten - Karolinska Institutet
Stanley L. Hazen - Cleveland Clinic
Jie Huang - Boston VA Research Institute
Mika Kahonen - Tampere University
Theodosios Kyriakou - University of Oxford
Reijo Laaksonen - Tampere University
Lars Lind - Uppsala University
Cecilia Lindgren - Wellcome Centre for Human Genetics
Patrik K. E. Magnusson - Karolinska Institutet
Eirini Marouli - Queen Mary University of London
Evelin Mihailov - University of Tartu
Andrew P. Morris - Wellcome Centre for Human Genetics
Kjell Nikus - Tampere University Hospital
Nancy Pedersen - Karolinska Institutet
Loukianos Rallidis - University General Hospital Attikon
Veikko Salomaa - Finnish Institute for Health and Welfare
Svati H. Shah - Duke University
Alexandre F. R. Stewart - Canadian Heart Research Centre
John R. Thompson - University of Leicester
Pierre A. Zalloua - Lebanese American University
John C. Chambers - Ealing Hospital
Rory Collins - University of Oxford
Erik Ingelsson - Wellcome Centre for Human Genetics
Carlos Iribarren - Kaiser Permanente
Pekka J. Karhunen - Fimlab
Jaspal S. Kooner - Imperial College London
Terho Lehtimaki - Fimlab
Ruth J. F. Loos - Icahn School of Medicine at Mount Sinai
Winfried Maerz - Heidelberg University
Ruth McPherson - University of Ottawa
Andres Metspalu - University of Tartu
Muredach P. Reilly - Cardiovascular Institute of the South
Samuli Ripatti - Kaiser Permanente
Dharambir K. Sanghera - University of Oklahoma Health Sciences Center
Joachim Thiery - University Hospital Leipzig
Hugh Watkins - University of Oxford
Panos Deloukas - Queen Mary University of London
Sekar Kathiresan - Broad Institute
Nilesh J. Samani - University of Leicester
Heribert Schunkert - German Centre for Cardiovascular Research
Jeanette Erdmann - German Centre for Cardiovascular Research
Inke R. Koenig - University of Lübeck
Publication Details: Scientific reports, Vol.6(1), pp.35278-35278
Publisher: NATURE PORTFOLIO
Number of pages: 9
Grant note: Tampere Tuberculosis Foundation 15POST23280019 / American Heart Association 01ZX1313A-2014 / German Federal Ministry of Education and Research (BMBF); Federal Ministry of Education & Research (BMBF) 9M048; 9N035 / Competitive Research Funding of the Tampere University Hospital German Federal Ministry of Education and Research (BMBF); Federal Ministry of Education & Research (BMBF) FP6-LIFESCIHEALTH / European Union Sixth Framework Programme FP6 (Cardiogenics); Marie Curie Actions British Heart Foundation NOT-HG-11-009 / National Genome Research Institute EU/QLRT-2001-01254; QLG2-CT-2002-01254 / GenomEUtwin Tampere University Foundation IUT20-60 / Estonian Research Council HEALTH-F2-2013-601456 / Seventh Framework Programme (CVgenes-at-target) HL095987; HL101621 / NIH grants; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA G0601966; G0700931 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 11966 / Canada Foundation for Innovation; CGIAR; Spanish Government 261433 / European Community's Seventh Framework Programme through the BioSHaRE-EU (Biobank Standardisation and Harmonisation for Research Excellence in the European Union) project LSHM-CT-2006-037593 / 6th Framework Program of the European Union 20120197 / Swedish Heart-Lung Foundation 01ZX1313A-2014 / e:Med research and funding concept (e:AtheroSysMed) Emil Aaltonen Foundation EU FP6 award Wissenschaftsoffensive TMO National Institute for Health Research; National Institutes of Health Research (NIHR) FS/14/55/30806; SP/04/002 / British Heart Foundation G0601966; G0700931 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) G51 / Action on Hearing Sigrid Juselius Foundation 213506; 129680 / Academy of Finland Center of Excellence in Complex Disease Genetics; Research Council of Finland INTERREG IV Oberrhein Program (Project A28) European Regional Development Fund (ERDF); Interreg Europe 2012-1397; M-2005-1112; 2009-2298 / Swedish Research Council; Swedish Research Council for Health Working Life & Welfare (Forte); Swedish Research Council Formas 251217; 285380 / Academy of Finland; Research Council of Finland DK088942 / NIDDK career development award ARENG SP1GV / University Tartu Fondation Leducq; Leducq Foundation Yrjo Jahnsson Foundation NF-SI-0611-10170 / National Institute for Health Research; National Institutes of Health Research (NIHR) R01HL087676 / US National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) HL087647 / NHLBI grant 3.2.0304.11-0312 / Research Roadmap Donovan Family Foundation National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust European Research Council (ERC Starting Grant); European Research Council (ERC) 2013-024 / Swedish Diabetes Foundation R01DK082766 / NIH grants - National Institute of Diabetes and Digestive and Kidney Diseases PENED 2003 / Greek General Secretary of Research and Technology Free State of Saxony NA6001; NA6650 / Heart & Stroke Foundation of Canada 560283 / Stockholm County Council European Union FP7 (EpiMigrant, 279143 / European Union FP7 (EpiMigrant) Strategic Cardiovascular Program of Karolinska Institutet and Stockholm County Council Finnish Foundation of Cardiovascular Research Andrea and Charles Bronfman Philanthropies Reynold's Foundation 07611; 084723/Z/08/Z; 090532/Z/09/Z / Wellcome Trust BHF Centre of Research Excellence Finnish Cultural Foundation; Finnish IT center for science U01HG007417 / NHGRI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) European Union; European Commission; Spanish Government Finnish Foundation for Cardiovascular Research Roche Vitamins Ltd RG/14/5/30893 / BHF grant Canadian Institute of Health Research and Natural Sciences and Engineering Research Council of Canada; Natural Sciences and Engineering Research Council of Canada (NSERC); Canadian Institutes of Health Research (CIHR) DK U01-066134 / NIH grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Knut and Alice Wallenberg Foundation; Knut & Alice Wallenberg Foundation AstraZeneca Torsten and Ragnar Soderberg Foundation 12CVD02 / Fondation Leducq (CADgenomics:Understanding CAD Genes); Leducq Foundation 201668; 305739 / EU's 7th Framework Programme LSHM-CT-2007-037273 / European Community Sixth Framework Program; European Commission European Regional Development Fund (ERDF); European Commission Foundation for Strategic Research Pirkanmaa Regional Fund of the Finnish Cultural Foundation FS/14/55/30806; RG/14/5/30893 / British Heart Foundation MGH Research Scholar Award Emil Aaltonen Foundation, Finland VPR Bridge grant from University of Oklahoma Health Sciences Center, Oklahoma City, USA Ministry for Higher Education Merck and Co; Merck & Company RP-PG-0407-10371 / NIHR; National Institutes of Health Research (NIHR) MOP-2380941; MOP82810; MOP77682 / Canadian Institutes of Health Research; Canadian Institutes of Health Research (CIHR) UK Medical Research Council (MRC); UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 9M048; 9N035; X51001 / Tampere University Hospital Medical Funds
Identifiers: 9936787508331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article