No association of coronary artery disease with x-chromosomal variants in comprehensive international meta-analysis

No association of coronary artery disease with x-chromosomal variants in comprehensive international meta-analysis

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 chromosom...

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Main Authors: Loley, C, Alver, M, Assimes, T, Bjonnes, A, Goel, A, Gustafsson, S, Hernesniemi, J, Hopewell, J, Kanoni, S, Kleber, M, Lau, K, Lu, Y, Lyytikäinen, L, Nelson, C, Nikpay, M, Qu, L, Salfati, E, Scholz, M, Tukiainen, T, Willenborg, C, Won, H, Zeng, L, Zhang, W, Anand, S, Beutner, F, Bottinger, E, Clarke, R, Dedoussis, G, Do, R, Esko, T, Eskola, M, Farrall, M, Gauguier, D, Giedraitis, V, Granger, C, Hall, A, Hamsten, A, Hazen, S, Huang, J, Kähönen, M, Kyriakou, T, Laaksonen, R, Lind, L, Lindgren, C, Magnusson, P, Marouli, E, Mihailov, E, Morris, A, Nikus, K, Pedersen, N, Rallidis, L, Salomaa, V, Shah, S, Stewart, A, Thompson, J, Zalloua, P, Chambers, J, Collins, R, Ingelsson, E, Iribarren, C, Karhunen, P, Kooner, J, Lehtimäki, T, Loos, R, März, W, McPherson, R, Metspalu, A, Reilly, M, Ripatti, S, Sanghera, D, Thiery, J, Watkins, H, Deloukas, P, Kathiresan, S, Samani, N, Schunkert, H, Erdmann, J, König, I
Format: Journal article
Language:English
Published: Springer Nature 2016
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Summary: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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