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 Lyytikaïnen, Christopher P. Nelson, Majid Nikpay, Liming Qu, Elias Salfati, Markus Scholz, Taru Tukiainen, Christina WillenborgHong Hee Won, Lingyao Zeng, Weihua Zhang, Sonia S. Anand, Frank Beutner, Erwin P. Bottinger, Robert Clarke, George Dedoussis, Ron Do, Toñu Esko, Markku Eskola, Martin Farrall, Dominique Gauguier, Vilmantas Giedraitis, Christopher B. Granger, Alistair S. Hall, Anders Hamsten, Stanley L. Hazen, Jie Huang, Mika Kähönen, 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 Lehtimäki, Ruth J.F. Loos, Winfried März, 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. König

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24 Scopus citations

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.

Original languageBritish English
Article number35278
JournalScientific Reports
Volume6
DOIs
StatePublished - 12 Oct 2016

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