No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis
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Author
Loley, Christina
Alver, Maris
Assimes, Themistocles L.
Bjonnes, Andrew
Goel, Anuj
Gustafsson, Stefan
Hernesniemi, Jussi
Hopewell, Jemma C.
Kanoni, Stavroula
Kleber, Marcus E.
Lau, King Wai
Lu, Yingchang
Lyytikäinen, Leo-Pekka
Nelson, Christopher P.
Nikpay, Majid
Qu, Liming
Salfati, Elias
Scholz, Markus
Tukiainen, Taru
Willenborg, Christina
Won, Hong-Hee
Zeng, Lingyao
Zhang, Weihua
Anand, Sonia S.
Beutner, Frank
Bottinger, Erwin P.
Clarke, Robert
Dedoussis, George
Do, Ron
Eskola, Markku
Farrall, Martin
Gauguier, Dominique
Giedraitis, Vilmantas
Granger, Christopher B.
Hall, Alistair S.
Hamsten, Anders
Hazen, Stanley L.
Huang, Jie
Kähönen, Mika
Kyriakou, Theodosios
Laaksonen, Reijo
Lind, Lars
Lindgren, Cecilia
Magnusson, Patrik K. E.
Marouli, Eirini
Mihailov, Evelin
Morris, Andrew P.
Nikus, Kjell
Pedersen, Nancy
Rallidis, Loukianos
Salomaa, Veikko
Shah, Svati H.
Stewart, Alexandre F. R.
Thompson, John R.
Chambers, John C.
Collins, Rory
Ingelsson, Erik
Iribarren, Carlos
Karhunen, Pekka J.
Kooner, Jaspal S.
Lehtimäki, Terho
Loos, Ruth J. F.
März, Winfried
McPherson, Ruth
Metspalu, Andres
Reilly, Muredach P.
Ripatti, Samuli
Sanghera, Dharambir K.
Thiery, Joachim
Watkins, Hugh
Deloukas, Panos
Kathiresan, Sekar
Samani, Nilesh J.
Schunkert, Heribert
Erdmann, Jeanette
König, Inke R.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/srep35278Metadata
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Loley, C., M. Alver, T. L. Assimes, A. Bjonnes, A. Goel, S. Gustafsson, J. Hernesniemi, et al. 2016. “No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis.” Scientific Reports 6 (1): 35278. doi:10.1038/srep35278. http://dx.doi.org/10.1038/srep35278.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5059659/pdf/Terms of Use
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