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Title: No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis.
Authors: Loley, C.
Alver, M.
Assimes, T. L.
Bjonnes, A.
Goel, A.
Gustafsson, S.
Hernesniemi, J.
Hopewell, J. C.
Kanoni, S.
Kleber, M. E.
Lau, K. W.
Lu, Y.
Lyytikäinen, L. P.
Nelson, Christopher P.
Nikpay, M.
Qu, L.
Salfati, E.
Scholz, M.
Tukiainen, T.
Willenborg, C.
Won, H. H.
Zeng, L.
Zhang, W.
Anand, S. S.
Beutner, F.
Bottinger, E. P.
Clarke, R.
Dedoussis, G.
Do, R.
Esko, T.
Eskola, M.
Farrall, M.
Gauguier, D.
Giedraitis, V.
Granger, C. B.
Hall, A. S.
Hamsten, A.
Hazen, S. L.
Huang, J.
Kähönen, M.
Kyriakou, T.
Laaksonen, R.
Lind, L.
Lindgren, C.
Magnusson, P. K.
Marouli, E.
Mihailov, E.
Morris, A. P.
Nikus, K.
Pedersen, N.
Rallidis, L.
Salomaa, V.
Shah, S. H.
Stewart, A. F.
Thompson, John R.
Zalloua, P. A.
Chambers, J. C.
Collins, R.
Ingelsson, E.
Iribarren, C.
Karhunen, P. J.
Kooner, J. S.
Lehtimäki, T.
Loos, R. J.
März, W.
McPherson, R.
Metspalu, A.
Reilly, M. P.
Ripatti, S.
Sanghera, D. K.
Thiery, J.
Watkins, H.
Deloukas, P.
Kathiresan, S.
Samani, Nilesh J.
Schunkert, H.
Erdmann, J.
König, I. R.
First Published: 12-Oct-2016
Publisher: Nature Publishing Group
Citation: Scientific Reports, 2016, 6:35278
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.
DOI Link: 10.1038/srep35278
ISSN: 2045-2322
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
Description: Supplementary information accompanies this paper at
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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