Gene-gene Interaction Analyses for Atrial Fibrillation

H Lin; M Mueller-Nurasyid; AV Smith; DE Arking; J Barnard; TM Bartz; KL Lunetta; K Lohman; ME Kleber; SA Lubitz; B Geelhoed; S Trompet; Marieke Niemeijer; T Kacprowski; DI Chasman; D Klarin; MF Sinner; M Waldenberger; T Meitinger; TB Harris; LJ Launer; EZ Soliman; LY Chen; JD Smith; DR Van Wagoner; JI Rotter; BM Psaty; Z Xie; AE Hendricks; J Ding; GE Delgado; N Verweij; P van der Harst; PW Macfarlane; I Ford; Bert Hofman; André Uitterlinden; Jan Heeringa; OH Franco Duran; Jan Kors; S Weiss; H Volzke; LM Rose; P Natarajan; S Kathiresan; S Kaab; V Gudnason; A Alonso; MK Chung; SR Heckbert; EJ Benjamin; Y Liu; W Marz; M Rienstra; JW Jukema; Bruno Stricker; M Dorr; CM Albert; PT Ellinor

doi:10.1038/srep35371

Gene-gene Interaction Analyses for Atrial Fibrillation

H Lin, M Mueller-Nurasyid, AV Smith, DE Arking, J Barnard, TM Bartz, KL Lunetta, K Lohman, ME Kleber, SA Lubitz, B Geelhoed, S Trompet, Marieke Niemeijer, T Kacprowski, DI Chasman, D Klarin, MF Sinner, M Waldenberger, T Meitinger, TB HarrisLJ Launer, EZ Soliman, LY Chen, JD Smith, DR Van Wagoner, JI Rotter, BM Psaty, Z Xie, AE Hendricks, J Ding, GE Delgado, N Verweij, P van der Harst, PW Macfarlane, I Ford, Bert Hofman, André Uitterlinden, Jan Heeringa, OH Franco Duran, Jan Kors, S Weiss, H Volzke, LM Rose, P Natarajan, S Kathiresan, S Kaab, V Gudnason, A Alonso, MK Chung, SR Heckbert, EJ Benjamin, Y Liu, W Marz, M Rienstra, JW Jukema, Bruno Stricker, M Dorr, CM Albert, PT Ellinor

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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 x 10(-8)). Eight additional gene-gene interactions were also marginally significant (P < 5 x 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 language	Undefined/Unknown
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep35371
Publication status	Published - 2016

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Lin, H., Mueller-Nurasyid, M., Smith, AV., Arking, DE., Barnard, J., Bartz, TM., Lunetta, KL., Lohman, K., Kleber, ME., Lubitz, SA., Geelhoed, B., Trompet, S., Niemeijer, M., Kacprowski, T., Chasman, DI., Klarin, D., Sinner, MF., Waldenberger, M., Meitinger, T., ... Ellinor, PT. (2016). Gene-gene Interaction Analyses for Atrial Fibrillation. Scientific Reports, 6. https://doi.org/10.1038/srep35371

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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 x 10(-8)). Eight additional gene-gene interactions were also marginally significant (P < 5 x 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 = "H Lin and M Mueller-Nurasyid and AV Smith and DE Arking and J Barnard and TM Bartz and KL Lunetta and K Lohman and ME Kleber and SA Lubitz and B Geelhoed and S Trompet and Marieke Niemeijer and T Kacprowski and DI Chasman and D Klarin and MF Sinner and M Waldenberger and T Meitinger and TB Harris and LJ Launer and EZ Soliman and LY Chen and JD Smith and {Van Wagoner}, DR and JI Rotter and BM Psaty and Z Xie and AE Hendricks and J Ding and GE Delgado and N Verweij and {van der Harst}, P and PW Macfarlane and I Ford and Bert Hofman and Andr{\'e} Uitterlinden and Jan Heeringa and {Franco Duran}, OH and Jan Kors and S Weiss and H Volzke and LM Rose and P Natarajan and S Kathiresan and S Kaab and V Gudnason and A Alonso and MK Chung and SR Heckbert and EJ Benjamin and Y Liu and W Marz and M Rienstra and JW Jukema and Bruno Stricker and M Dorr and CM Albert and PT Ellinor",

year = "2016",

doi = "10.1038/srep35371",

language = "Undefined/Unknown",

volume = "6",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

}

Lin, H, Mueller-Nurasyid, M, Smith, AV, Arking, DE, Barnard, J, Bartz, TM, Lunetta, KL, Lohman, K, Kleber, ME, Lubitz, SA, Geelhoed, B, Trompet, S, Niemeijer, M, 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, B , Uitterlinden, A, Heeringa, J, Franco Duran, OH, Kors, J, Weiss, S, Volzke, H, Rose, LM, Natarajan, P, Kathiresan, S, Kaab, S, Gudnason, V, Alonso, A, Chung, MK, Heckbert, SR, Benjamin, EJ, Liu, Y, Marz, W, Rienstra, M, Jukema, JW, Stricker, B, Dorr, M, Albert, CM & Ellinor, PT 2016, 'Gene-gene Interaction Analyses for Atrial Fibrillation', Scientific Reports, vol. 6. https://doi.org/10.1038/srep35371

TY - JOUR

T1 - Gene-gene Interaction Analyses for Atrial Fibrillation

AU - Lin, H

AU - Mueller-Nurasyid, M

AU - Smith, AV

AU - Arking, DE

AU - Barnard, J

AU - Bartz, TM

AU - Lunetta, KL

AU - Lohman, K

AU - Kleber, ME

AU - Lubitz, SA

AU - Geelhoed, B

AU - Trompet, S

AU - Niemeijer, Marieke

AU - Kacprowski, T

AU - Chasman, DI

AU - Klarin, D

AU - Sinner, MF

AU - Waldenberger, M

AU - Meitinger, T

AU - Harris, TB

AU - Launer, LJ

AU - Soliman, EZ

AU - Chen, LY

AU - Smith, JD

AU - Van Wagoner, DR

AU - Rotter, JI

AU - Psaty, BM

AU - Xie, Z

AU - Hendricks, AE

AU - Ding, J

AU - Delgado, GE

AU - Verweij, N

AU - van der Harst, P

AU - Macfarlane, PW

AU - Ford, I

AU - Hofman, Bert

AU - Uitterlinden, André

AU - Heeringa, Jan

AU - Franco Duran, OH

AU - Kors, Jan

AU - Weiss, S

AU - Volzke, H

AU - Rose, LM

AU - Natarajan, P

AU - Kathiresan, S

AU - Kaab, S

AU - Gudnason, V

AU - Alonso, A

AU - Chung, MK

AU - Heckbert, SR

AU - Benjamin, EJ

AU - Liu, Y

AU - Marz, W

AU - Rienstra, M

AU - Jukema, JW

AU - Stricker, Bruno

AU - Dorr, M

AU - Albert, CM

AU - Ellinor, PT

PY - 2016

Y1 - 2016

N2 - 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 x 10(-8)). Eight additional gene-gene interactions were also marginally significant (P < 5 x 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.

AB - 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 x 10(-8)). Eight additional gene-gene interactions were also marginally significant (P < 5 x 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.

U2 - 10.1038/srep35371

DO - 10.1038/srep35371

M3 - Article

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

ER -