Gene-gene Interaction Analyses for Atrial Fibrillation

Honghuang Lin, Martina Mueller-Nurasyid, Albert V. Smith, Dan Arking, John Barnard, Traci M. Bartz, Kathryn L. Lunetta, Kurt Lohman, Marcus E. Kleber, Steven A. Lubitz, Bastiaan Geelhoed, Stella Trompet, Maartje N. Niemeijer, Tim Kacprowski, Daniel I. Chasman, Derek Klarin, Moritz F. Sinner, Melanie Waldenberger, Thomas Meitinger, Tamara B. HarrisLenore J. Launer, Elsayed Z. Soliman, Lin Y. Chen, Jonathan D. Smith, David R. Van Wagoner, Jerome I. Rotter, Bruce M. Psaty, Zhijun Xie, Audrey E. Hendricks, Jingzhong Ding, Graciela E. Delgado, Niek Verweij, Pim Van Der Harst, Peter W. Macfarlane, Ian Ford, Albert Hofman, André Uitterlinden, Jan Heeringa, Oscar H. Franco, Jan A. Kors, Stefan Weiss, Henry Völzke, Lynda M. Rose, Pradeep Natarajan, Sekar Kathiresan, Stefan Kääb, Vilmundur Gudnason, Alvaro Alonso, Mina K. Chung, Susan R. Heckbert, Emelia J. Benjamin, Yongmei Liu, Winfried März, Michiel Rienstra, J. Wouter Jukema, Bruno H. Stricker, Marcus Dörr, Christine M. Albert, Patrick T. Ellinor

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number35371
JournalScientific Reports
Volume6
DOIs
StatePublished - Nov 8 2016

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Atrial Fibrillation
Genes
Single Nucleotide Polymorphism
Sample Size
Genome

ASJC Scopus subject areas

  • General

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Lin, H., Mueller-Nurasyid, M., Smith, A. V., Arking, D., Barnard, J., Bartz, T. M., ... Ellinor, P. T. (2016). Gene-gene Interaction Analyses for Atrial Fibrillation. Scientific Reports, 6, [35371]. https://doi.org/10.1038/srep35371

Gene-gene Interaction Analyses for Atrial Fibrillation. / Lin, Honghuang; Mueller-Nurasyid, Martina; Smith, Albert V.; Arking, Dan; Barnard, John; Bartz, Traci M.; Lunetta, Kathryn L.; Lohman, Kurt; Kleber, Marcus E.; Lubitz, Steven A.; Geelhoed, Bastiaan; Trompet, Stella; Niemeijer, Maartje N.; Kacprowski, Tim; Chasman, Daniel I.; Klarin, Derek; Sinner, Moritz F.; Waldenberger, Melanie; Meitinger, Thomas; Harris, Tamara B.; Launer, Lenore J.; Soliman, Elsayed Z.; Chen, Lin Y.; Smith, Jonathan D.; Van Wagoner, David R.; Rotter, Jerome I.; Psaty, Bruce M.; Xie, Zhijun; Hendricks, Audrey E.; Ding, Jingzhong; Delgado, Graciela E.; Verweij, Niek; Van Der Harst, Pim; Macfarlane, Peter W.; Ford, Ian; Hofman, Albert; Uitterlinden, André; Heeringa, Jan; Franco, Oscar H.; Kors, Jan A.; Weiss, Stefan; Völzke, Henry; Rose, Lynda M.; Natarajan, Pradeep; Kathiresan, Sekar; Kääb, Stefan; Gudnason, Vilmundur; Alonso, Alvaro; Chung, Mina K.; Heckbert, Susan R.; Benjamin, Emelia J.; Liu, Yongmei; März, Winfried; Rienstra, Michiel; Jukema, J. Wouter; Stricker, Bruno H.; Dörr, Marcus; Albert, Christine M.; Ellinor, Patrick T.

In: Scientific Reports, Vol. 6, 35371, 08.11.2016.

Research output: Contribution to journalArticle

Lin, H, Mueller-Nurasyid, M, Smith, AV, Arking, D, Barnard, J, Bartz, TM, Lunetta, KL, Lohman, K, Kleber, ME, Lubitz, SA, Geelhoed, B, Trompet, S, Niemeijer, MN, Kacprowski, T, Chasman, DI, Klarin, D, Sinner, MF, Waldenberger, M, Meitinger, T, Harris, TB, Launer, LJ, Soliman, EZ, Chen, LY, Smith, JD, Van Wagoner, DR, Rotter, JI, Psaty, BM, Xie, Z, Hendricks, AE, Ding, J, Delgado, GE, Verweij, N, Van Der Harst, P, Macfarlane, PW, Ford, I, Hofman, A, Uitterlinden, A, Heeringa, J, Franco, OH, Kors, JA, Weiss, S, Völzke, H, Rose, LM, Natarajan, P, Kathiresan, S, Kääb, S, Gudnason, V, Alonso, A, Chung, MK, Heckbert, SR, Benjamin, EJ, Liu, Y, März, W, Rienstra, M, Jukema, JW, Stricker, BH, Dörr, M, Albert, CM & Ellinor, PT 2016, 'Gene-gene Interaction Analyses for Atrial Fibrillation', Scientific Reports, vol. 6, 35371. https://doi.org/10.1038/srep35371
Lin H, Mueller-Nurasyid M, Smith AV, Arking D, Barnard J, Bartz TM et al. Gene-gene Interaction Analyses for Atrial Fibrillation. Scientific Reports. 2016 Nov 8;6. 35371. https://doi.org/10.1038/srep35371
Lin, Honghuang ; Mueller-Nurasyid, Martina ; Smith, Albert V. ; Arking, Dan ; Barnard, John ; Bartz, Traci M. ; Lunetta, Kathryn L. ; Lohman, Kurt ; Kleber, Marcus E. ; Lubitz, Steven A. ; Geelhoed, Bastiaan ; Trompet, Stella ; Niemeijer, Maartje N. ; Kacprowski, Tim ; Chasman, Daniel I. ; Klarin, Derek ; Sinner, Moritz F. ; Waldenberger, Melanie ; Meitinger, Thomas ; Harris, Tamara B. ; Launer, Lenore J. ; Soliman, Elsayed Z. ; Chen, Lin Y. ; Smith, Jonathan D. ; Van Wagoner, David R. ; Rotter, Jerome I. ; Psaty, Bruce M. ; Xie, Zhijun ; Hendricks, Audrey E. ; Ding, Jingzhong ; Delgado, Graciela E. ; Verweij, Niek ; Van Der Harst, Pim ; Macfarlane, Peter W. ; Ford, Ian ; Hofman, Albert ; Uitterlinden, André ; Heeringa, Jan ; Franco, Oscar H. ; Kors, Jan A. ; Weiss, Stefan ; Völzke, Henry ; Rose, Lynda M. ; Natarajan, Pradeep ; Kathiresan, Sekar ; Kääb, Stefan ; Gudnason, Vilmundur ; Alonso, Alvaro ; Chung, Mina K. ; Heckbert, Susan R. ; Benjamin, Emelia J. ; Liu, Yongmei ; März, Winfried ; Rienstra, Michiel ; Jukema, J. Wouter ; Stricker, Bruno H. ; Dörr, Marcus ; Albert, Christine M. ; Ellinor, Patrick T. / Gene-gene Interaction Analyses for Atrial Fibrillation. In: Scientific Reports. 2016 ; Vol. 6.
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title = "Gene-gene Interaction Analyses for Atrial Fibrillation",
abstract = "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.",
author = "Honghuang Lin and Martina Mueller-Nurasyid and Smith, {Albert V.} and Dan Arking and John Barnard and Bartz, {Traci M.} and Lunetta, {Kathryn L.} and Kurt Lohman and Kleber, {Marcus E.} and Lubitz, {Steven A.} and Bastiaan Geelhoed and Stella Trompet and Niemeijer, {Maartje N.} and Tim Kacprowski and Chasman, {Daniel I.} and Derek Klarin and Sinner, {Moritz F.} and Melanie Waldenberger and Thomas Meitinger and Harris, {Tamara B.} and Launer, {Lenore J.} and Soliman, {Elsayed Z.} and Chen, {Lin Y.} and Smith, {Jonathan D.} and {Van Wagoner}, {David R.} and Rotter, {Jerome I.} and Psaty, {Bruce M.} and Zhijun Xie and Hendricks, {Audrey E.} and Jingzhong Ding and Delgado, {Graciela E.} and Niek Verweij and {Van Der Harst}, Pim and Macfarlane, {Peter W.} and Ian Ford and Albert Hofman and Andr{\'e} Uitterlinden and Jan Heeringa and Franco, {Oscar H.} and Kors, {Jan A.} and Stefan Weiss and Henry V{\"o}lzke and Rose, {Lynda M.} and Pradeep Natarajan and Sekar Kathiresan and Stefan K{\"a}{\"a}b and Vilmundur Gudnason and Alvaro Alonso and Chung, {Mina K.} and Heckbert, {Susan R.} and Benjamin, {Emelia J.} and Yongmei Liu and Winfried M{\"a}rz and Michiel Rienstra and Jukema, {J. Wouter} and Stricker, {Bruno H.} and Marcus D{\"o}rr and Albert, {Christine M.} and Ellinor, {Patrick T.}",
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T1 - Gene-gene Interaction Analyses for Atrial Fibrillation

AU - Lin, Honghuang

AU - Mueller-Nurasyid, Martina

AU - Smith, Albert V.

AU - Arking, Dan

AU - Barnard, John

AU - Bartz, Traci M.

AU - Lunetta, Kathryn L.

AU - Lohman, Kurt

AU - Kleber, Marcus E.

AU - Lubitz, Steven A.

AU - Geelhoed, Bastiaan

AU - Trompet, Stella

AU - Niemeijer, Maartje N.

AU - Kacprowski, Tim

AU - Chasman, Daniel I.

AU - Klarin, Derek

AU - Sinner, Moritz F.

AU - Waldenberger, Melanie

AU - Meitinger, Thomas

AU - Harris, Tamara B.

AU - Launer, Lenore J.

AU - Soliman, Elsayed Z.

AU - Chen, Lin Y.

AU - Smith, Jonathan D.

AU - Van Wagoner, David R.

AU - Rotter, Jerome I.

AU - Psaty, Bruce M.

AU - Xie, Zhijun

AU - Hendricks, Audrey E.

AU - Ding, Jingzhong

AU - Delgado, Graciela E.

AU - Verweij, Niek

AU - Van Der Harst, Pim

AU - Macfarlane, Peter W.

AU - Ford, Ian

AU - Hofman, Albert

AU - Uitterlinden, André

AU - Heeringa, Jan

AU - Franco, Oscar H.

AU - Kors, Jan A.

AU - Weiss, Stefan

AU - Völzke, Henry

AU - Rose, Lynda M.

AU - Natarajan, Pradeep

AU - Kathiresan, Sekar

AU - Kääb, Stefan

AU - Gudnason, Vilmundur

AU - Alonso, Alvaro

AU - Chung, Mina K.

AU - Heckbert, Susan R.

AU - Benjamin, Emelia J.

AU - Liu, Yongmei

AU - März, Winfried

AU - Rienstra, Michiel

AU - Jukema, J. Wouter

AU - Stricker, Bruno H.

AU - Dörr, Marcus

AU - Albert, Christine M.

AU - Ellinor, Patrick T.

PY - 2016/11/8

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