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No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis
Univ Lubeck, Univ Klinikum Schleswig Holstein, Inst Med Biometrie & Stat, Campus Lubeck, Lubeck, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Hamburg Lubeck Kiel, Lubeck, Germany..
Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Inst Mol & Cell Biol, Tartu, Estonia..
Stanford Univ, Sch Med Stanford, Dept Med, Div Cardiovasc Med, Stanford, CA USA..
Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA..
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2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 35278Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2016. Vol. 6, 35278
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:uu:diva-307543DOI: 10.1038/srep35278ISI: 000385004200001PubMedID: 27731410OAI: oai:DiVA.org:uu-307543DiVA: diva2:1047269
Funder
EU, European Research Council, LSHM-CT-2006-037593 FP6-LIFESCIHEALTH LSHM-CT-2007-037273NIH (National Institute of Health), HL095987 HL101621 R01DK082766 DK U01-066134EU, FP7, Seventh Framework Programme, HEALTH-F2-2013-601456 201668 305739 European Union FP7 (EpiMigrant, 279143 261433Wellcome trust, 07611 084723/Z/08/Z 090532/Z/09/ZKnut and Alice Wallenberg FoundationSwedish Diabetes Association, 2013-024Swedish Research Council, 2012-1397 M-2005-1112 2009-2298Swedish Heart Lung Foundation, 20120197AstraZenecaTorsten Söderbergs stiftelseRagnar Söderbergs stiftelseSwedish Foundation for Strategic Research Stockholm County Council, 560283
Available from: 2016-11-17 Created: 2016-11-17 Last updated: 2016-11-17Bibliographically approved

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