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

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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 , Lyytikainen , L-P , Nelson , C 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 , Kahonen , M , Kyriakou , T , Laaksonen , R , Lind , L , Lindgren , C , Magnusson , P K E , Marouli , E , Mihailov , E , Morris , A P , Nikus , K , Pedersen , N , Rallidis , L , Salomaa , V , Shah , S H , Stewart , A F R , Thompson , J R , Zalloua , P A , Chambers , J C , Collins , R , Ingelsson , E , Iribarren , C , Karhunen , P J , Kooner , J S , Lehtimaki , T , Loos , R J F , Maerz , W , McPherson , R , Metspalu , A , Reilly , M P , Ripatti , S , Sanghera , D K , Thiery , J , Watkins , H , Deloukas , P , Kathiresan , S , Samani , N J , Schunkert , H , Erdmann , J & Koenig , I R 2016 , ' No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis ' , Scientific Reports , vol. 6 , 35278 . https://doi.org/10.1038/srep35278

Title: No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis
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; Lyytikainen, 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; Esko, Tonu; Eskola, Markku; Farrall, Martin; Gauguier, Dominique; Giedraitis, Vilmantas; Granger, Christopher B.; Hall, Alistair S.; Hamsten, Anders; Hazen, Stanley L.; Huang, Jie; Kahonen, 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.; Zalloua, Pierre A.; Chambers, John C.; Collins, Rory; Ingelsson, Erik; Iribarren, Carlos; Karhunen, Pekka J.; Kooner, Jaspal S.; Lehtimaki, Terho; Loos, Ruth J. F.; Maerz, 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; Koenig, Inke R.
Contributor: University of Helsinki, Massachusetts General Hospital
University of Helsinki, Clinicum
Date: 2016-10-12
Language: eng
Number of pages: 9
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/168823
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.
Subject: GENOME-WIDE ASSOCIATION
GENOTYPE IMPUTATION
INACTIVATION
SEX
3111 Biomedicine
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