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Genome-Wide Interaction Analyses of Serum Calcium on Ventricular Repolarization Time in 125 393 Participants.

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Τίτλος: Genome-Wide Interaction Analyses of Serum Calcium on Ventricular Repolarization Time in 125 393 Participants.
Συγγραφείς: Young, WJ, van der Most, PJ, Bartz, TM, Bos, MM, Biino, G, Duong, T, Foco, L, Lominchar, JT, Müller-Nurasyid, M, Nardone, GG, Pecori, A, Ramirez, J, Repetto, L, Schramm, K, Shen, X, van Duijvenboden, S, van Heemst, D, Weiss, S, Yao, J, Benjamins, J-W, Alonso, A, Spedicati, B, Biggs, ML, Brody, JA, Dörr, M, Fuchsberger, C, Gögele, M, Guo, X, Ikram, MA, Jukema, JW, Kääb, S, Kanters, JK, Lifelines Cohort Study, Lin, HJ, Linneberg, A, Nauck, M, Nolte, IM, Pianigiani, G, Santin, A, Soliman, EZ, Tesolin, P, Vaccargiu, S, Waldenberger, M, van der Harst, P, Verweij, N, Arking, DE, Concas, MP, De Grandi, A, Girotto, G, Grarup, N, Kavousi, M, Mook-Kanamori, DO, Navarro, P, Orini, M, Padmanabhan, S, Pattaro, C, Peters, A, Pirastu, M, Pramstaller, PP, Heckbert, SR, Sinner, M, Snieder, H, Völker, U, Wilson, JF, Gauderman, WJ, Lambiase, PD, Sotoodehnia, N, Tinker, A, Warren, HR, Noordam, R, Munroe, PB
Στοιχεία εκδότη: Wiley
Έτος έκδοσης: 2024
Συλλογή: Queen Mary University of London: Queen Mary Research Online (QMRO)
Θεματικοί όροι: ECG intervals, calcium, gene‐lifestyle interaction, genome‐wide association study, ventricular repolarization, Humans, Action Potentials, Arrhythmias, Cardiac, Electrocardiography, Genetic Predisposition to Disease, Genome-Wide Association Study, Heart Rate, Polymorphism, Single Nucleotide, Risk Factors, Time Factors
Περιγραφή: BACKGROUND: Ventricular repolarization time (ECG QT and JT intervals) is associated with malignant arrhythmia. Genome-wide association studies have identified 230 independent loci for QT and JT; however, 50% of their heritability remains unexplained. Previous work supports a causal effect of lower serum calcium concentrations on longer ventricular repolarization time. We hypothesized calcium interactions with QT and JT variant associations could explain a proportion of the missing heritability. METHODS AND RESULTS: We performed genome-wide calcium interaction analyses for QT and JT intervals. Participants were stratified by their calcium level relative to the study distribution (top or bottom 20%). We performed a 2-stage analysis (genome-wide discovery [N=62 532] and replication [N=59 861] of lead variants) and a single-stage genome-wide meta-analysis (N=122 393, [European ancestry N=117 581, African ancestry N=4812]). We also calculated 2-degrees of freedom joint main and interaction and 1-degree of freedom interaction P values. In 2-stage and single-stage analyses, 50 and 98 independent loci, respectively, were associated with either QT or JT intervals (2-degrees of freedom joint main and interaction P value <5×10-8). No lead variant had a significant interaction result after correcting for multiple testing and sensitivity analyses provided similar findings. Two loci in the single-stage meta-analysis were not reported previously (SPPL2B and RFX6). CONCLUSIONS: We have found limited support for an interaction effect of serum calcium on QT and JT variant associations despite sample sizes with suitable power to detect relevant effects. Therefore, such effects are unlikely to explain a meaningful proportion of the heritability of QT and JT, and factors including rare variation and other environmental interactions need to be considered.
Τύπος εγγράφου: article in journal/newspaper
Περιγραφή αρχείου: e034760 - ?
Γλώσσα: English
Relation: J Am Heart Assoc; https://qmro.qmul.ac.uk/xmlui/handle/123456789/99885
DOI: 10.1161/JAHA.123.034760
Διαθεσιμότητα: https://qmro.qmul.ac.uk/xmlui/handle/123456789/99885
https://doi.org/10.1161/JAHA.123.034760
Rights: This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. ; © 2024 The Author(s). Published on behalf of the American Heart Association, Inc., by Wiley.
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  Data: 2024
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  Data: Queen Mary University of London: Queen Mary Research Online (QMRO)
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  Data: BACKGROUND: Ventricular repolarization time (ECG QT and JT intervals) is associated with malignant arrhythmia. Genome-wide association studies have identified 230 independent loci for QT and JT; however, 50% of their heritability remains unexplained. Previous work supports a causal effect of lower serum calcium concentrations on longer ventricular repolarization time. We hypothesized calcium interactions with QT and JT variant associations could explain a proportion of the missing heritability. METHODS AND RESULTS: We performed genome-wide calcium interaction analyses for QT and JT intervals. Participants were stratified by their calcium level relative to the study distribution (top or bottom 20%). We performed a 2-stage analysis (genome-wide discovery [N=62 532] and replication [N=59 861] of lead variants) and a single-stage genome-wide meta-analysis (N=122 393, [European ancestry N=117 581, African ancestry N=4812]). We also calculated 2-degrees of freedom joint main and interaction and 1-degree of freedom interaction P values. In 2-stage and single-stage analyses, 50 and 98 independent loci, respectively, were associated with either QT or JT intervals (2-degrees of freedom joint main and interaction P value &lt;5&#215;10-8). No lead variant had a significant interaction result after correcting for multiple testing and sensitivity analyses provided similar findings. Two loci in the single-stage meta-analysis were not reported previously (SPPL2B and RFX6). CONCLUSIONS: We have found limited support for an interaction effect of serum calcium on QT and JT variant associations despite sample sizes with suitable power to detect relevant effects. Therefore, such effects are unlikely to explain a meaningful proportion of the heritability of QT and JT, and factors including rare variation and other environmental interactions need to be considered.
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  Data: J Am Heart Assoc; https://qmro.qmul.ac.uk/xmlui/handle/123456789/99885
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  Data: 10.1161/JAHA.123.034760
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  Data: https://qmro.qmul.ac.uk/xmlui/handle/123456789/99885&lt;br /&gt;https://doi.org/10.1161/JAHA.123.034760
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  Data: This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. ; &#169; 2024 The Author(s). Published on behalf of the American Heart Association, Inc., by Wiley.
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        Value: 10.1161/JAHA.123.034760
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      – Text: English
    Subjects:
      – SubjectFull: ECG intervals
        Type: general
      – SubjectFull: calcium
        Type: general
      – SubjectFull: gene‐lifestyle interaction
        Type: general
      – SubjectFull: genome‐wide association study
        Type: general
      – SubjectFull: ventricular repolarization
        Type: general
      – SubjectFull: Humans
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      – SubjectFull: Action Potentials
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      – SubjectFull: Arrhythmias
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      – SubjectFull: Cardiac
        Type: general
      – SubjectFull: Electrocardiography
        Type: general
      – SubjectFull: Genetic Predisposition to Disease
        Type: general
      – SubjectFull: Genome-Wide Association Study
        Type: general
      – SubjectFull: Heart Rate
        Type: general
      – SubjectFull: Polymorphism
        Type: general
      – SubjectFull: Single Nucleotide
        Type: general
      – SubjectFull: Risk Factors
        Type: general
      – SubjectFull: Time Factors
        Type: general
    Titles:
      – TitleFull: Genome-Wide Interaction Analyses of Serum Calcium on Ventricular Repolarization Time in 125 393 Participants.
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              M: 01
              Type: published
              Y: 2024
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              Value: edsbas.oa
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