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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-12

AUTHORS

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 Lyytikäinen, 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, Tõnu 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

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. More... »

PAGES

35278

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep35278

DOI

http://dx.doi.org/10.1038/srep35278

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1033795670

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27731410


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40 schema:description 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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