Gene-gene interaction analyses for atrial fibrillation

Lin, H. et al. (2016) Gene-gene interaction analyses for atrial fibrillation. Scientific Reports, 6, 35371. (doi: 10.1038/srep35371) (PMID:27824142) (PMCID:PMC5099695)

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Atrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility. We performed a large-scale association analysis of gene-gene interactions with AF in 8,173 AF cases, and 65,237 AF-free referents collected from 15 studies for discovery. We examined putative interactions between genome-wide SNPs and 17 known AF-related SNPs. The top interactions were then tested for association in an independent cohort for replication, which included more than 2,363 AF cases and 114,746 AF-free referents. One interaction, between rs7164883 at the HCN4 locus and rs4980345 at the SLC28A1 locus, was found to be significantly associated with AF in the discovery cohorts (interaction OR = 1.44, 95% CI: 1.27–1.65, P = 4.3 × 10–8). Eight additional gene-gene interactions were also marginally significant (P < 5 × 10–7). However, none of the top interactions were replicated. In summary, we did not find significant interactions that were associated with AF susceptibility. Future increases in sample size and denser genotyping might facilitate the identification of gene-gene interactions associated with AF.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Macfarlane, Professor Peter and Ford, Professor Ian
Authors: Lin, H., Mueller-Nurasyid, M., Smith, A. V., Arking, D. E., Barnard, J., Bartz, T. M., Lunetta, K. L., Lohman, K., Kleber, M. E., Lubitz, S. A., Geelhoed, B., Trompet, S., Niemeijer, M. N., Kacprowski, T., Chasman, D. I., Klarin, D., Sinner, M. F., Waldenberger, M., Meitinger, T., Harris, T. B., Launer, L. J., Soliman, E. Z., Chen, L. Y., Smith, J. D., Van Wagoner, D. R., Rotter, J. I., Psaty, B. M., Xie, Z., Hendricks, A. E., Ding, J., Delgado, G. E., Verweij, N., van der Harst, P., Macfarlane, P. W., Ford, I., Hofman, A., Uitterlinden, A., Heeringa, J., Franco, O. H., Kors, J. A., Weiss, S., Völzke, H., Rose, L. M., Natarajan, P., Kathiresan, S., Kääb, S., Gudnason, V., Alonso, A., Chung, M. K., Heckbert, S. R., Benjamin, E. J., Liu, Y., März, W., Rienstra, M., Jukema, J. W., Stricker, B. H., Dörr, M., Albert, C. M., and Ellinor, P. T.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
Journal Name:Scientific Reports
Publisher:Nature Publishing Group
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Scientific Reports 6: 35371
Publisher Policy:Reproduced under a Creative Commons License

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