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 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.
Loley, C; Alver, M; Assimes, TL; Bjonnes, A; Goel, A; Gustafsson, S; Hernesniemi, J; Hopewell, JC; Kanoni, S; Kleber, ME; Lau, KW; Lu, Y; Lyytikäinen, L-P; Nelson, CP; Nikpay, M; Qu, L; Salfati, E; Scholz, M; Tukiainen, T; Willenborg, C; Won, H-H; Zeng, L; Zhang, W; Anand, SS; Beutner, F; Bottinger, EP; Clarke, R; Dedoussis, G; Do, R; Esko, T; Eskola, M; Farrall, M; Gauguier, D; Giedraitis, V; Granger, CB; Hall, AS; Hamsten, A; Hazen, SL; Huang, J; Kähönen, M; Kyriakou, T; Laaksonen, R; Lind, L; Lindgren, C; Magnusson, PKE; Marouli, E; Mihailov, E; Morris, AP; Nikus, K; Pedersen, N; Rallidis, L; Salomaa, V; Shah, SH; Stewart, AFR; Thompson, JR; Zalloua, PA; Chambers, JC; Collins, R; Ingelsson, E; Iribarren, C; Karhunen, PJ; Kooner, JS; Lehtimäki, T; Loos, RJF; März, W; McPherson, R; Metspalu, A; Reilly, MP; Ripatti, S; Sanghera, DK; Thiery, J; Watkins, H; Deloukas, P; Kathiresan, S; Samani, NJ; Schunkert, H; Erdmann, J; König, IR
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