This research assessed the causal influence of atrial fibrillation (AF) on depression.
Methods
A two-sample Mendelian randomization (MR) approach was utilized along with data from additional databases. A genome-wide association study (GWAS) involving 463,010 participants allowed for the exploration of genetic variations associated with AF. Another GWAS with 215,644 individuals offered insights into the relationship between gene variants and depression. Data on the correlation between gene variants and depression were obtained from another GWAS encompassing 449,414 individuals. Effect sizes were assessed utilizing the inverse-variance weighted technique. Sensitivity analysis was conducted by weighted median, outlier, MR pleiotropy residual sum, weighted mode, and MR-Egger. A meta-analysis of the inverse-variance weighted (IVW) results from the two datasets was conducted.
Results
A significant association was found between genetically predicted AF and increased incidence of depression using 15 single nucleotide polymorphisms (SNPs) as markers. No evidence of gene pleiotropy was detected, as indicated by MR-Egger. Sensitivity analyses employing alternative Mendelian randomization techniques consistently yielded robust results. The combined odds ratio for depression was estimated at 29.19 (95% CI = 4.43-192.13, P < 0.001).
Conclusion
This study found a causal relationship between genetically predicted AF and a heightened risk of depression.
PatelMRMahaffeyKWGargJ, et al.Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883-891.
2.
BenjaminEJThomasKLGoAS, et al.Transforming atrial fibrillation research to integrate social determinants of health: a national heart, lung, and blood institute workshop report. JAMA Cardiol. 2023;8:182-191.
3.
López-LópezJASterneJACThomHHZ, et al.Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis. BMJ (Int Ed). 2017;359:j5058.
4.
BenjaminEJWolfPAD’AgostinoRBSilbershatzHKannelWBLevyD. Impact of atrial fibrillation on the risk of death: the framingham heart study. Circulation. 1998;98:946-952.
5.
LipGYHProiettiMPotparaT, et al.Atrial fibrillation and stroke prevention: 25 years of research at. EP Europace journal. Europace. 2023;25:euad226.
6.
RivardLFribergLConenD, et al.Atrial fibrillation and dementia: a report from the AF-SCREEN international collaboration. Circulation. 2022;145:392-409.
7.
FrederiksenTCDahmCCPreisSR, et al.The bidirectional association between atrial fibrillation and myocardial infarction. Nat Rev Cardiol. 2023;20:631-644.
8.
FauchierLBissonABodinA. Heart failure with preserved ejection fraction and atrial fibrillation: recent advances and open questions. BMC Med. 2023;21:54.
9.
BennM. Atrial fibrillation and chronic kidney disease. Eur Heart J. 2021;42:2824-2826.
10.
VitalisAShantsilaAProiettiM, et al.Peripheral arterial disease in patients with atrial fibrillation: the AFFIRM study. Am J Med. 2021;134:514-518.
11.
WaldmannVJouvenXNarayananK, et al.Association between atrial fibrillation and sudden cardiac death: pathophysiological and epidemiological insights. Circ Res. 2020;127:301-309.
12.
LiuQHeHYangJFengXZhaoFLyuJ. Changes in the global burden of depression from 1990 to 2017: findings from the global burden of disease study. J Psychiatr Res. 2020;126:134-140.
13.
RibeiroJDHuangXFoxKRFranklinJC. Depression and hopelessness as risk factors for suicide ideation, attempts and death: meta-analysis of longitudinal studies. Br J Psychiatry. 2018;212:279-286.
14.
HawtonKCasañasIComabellaCHawCSaundersK. Risk factors for suicide in individuals with depression: a systematic review. J Affect Disord. 2013;147:17-28.
15.
SenooKYukawaAOhkuraT, et al.Depression and quality of life in older adults with atrial fibrillation: a cross-sectional community-based study. Geriatr Gerontol Int. 2022;22:505-510.
16.
DąbrowskiRSmolis-BąkEKowalikIKazimierskaBWójcickaMSzwedH. Quality of life and depression in patients with different patterns of atrial fibrillation. Kardiol Pol. 2010;68:1133-1139.
17.
SchnabelRBMichalMWildeS, et al.Depression in atrial fibrillation in the general population. PLoS One. 2013;8:e79109.
18.
JaakkolaJTeppoKBiancariF, et al.The effect of mental health conditions on the use of oral anticoagulation therapy in patients with atrial fibrillation: the FinACAF study. Eur Heart J Qual Care Clin Outcomes. 2022;8:269-276.
19.
TeppoKJaakkolaJBiancariF, et al.Mental health conditions and use of rhythm control therapies in patients with atrial fibrillation: a nationwide cohort study. BMJ Open. 2022;12:e059759.
20.
TeppoKJaakkolaJLehtoMBiancariFAiraksinenKEJ. The impact of mental health conditions on oral anticoagulation therapy and outcomes in patients with atrial fibrillation: a systematic review and meta-analysis. Am J Prev Cardiol. 2021;7:100221.
21.
LarssonSCButterworthASBurgessS. Mendelian randomization for cardiovascular diseases: principles and applications. Eur Heart J. 2023;44:4913-4924.
22.
BurgessSDavey SmithGDaviesNM, et al.Guidelines for performing Mendelian randomization investigations: update for summer 2023. Wellcome Open Res. 2019;4:186.
SekulaPDel GrecoMFPattaroCKöttgenA. Mendelian randomization as an approach to assess causality using observational data. J Am Soc Nephrol. 2016;27:3253-3265.
25.
SkrivankovaVWRichmondRCWoolfBAR, et al.Strengthening the reporting of observational studies in epidemiology using mendelian randomisation (STROBE-MR): explanation and elaboration. BMJ (Int Ed). 2021;375:n2233.
KurkiMIKarjalainenJPaltaP, et al.FinnGen provides genetic insights from a well-phenotyped isolated population. Nature. 2023;613:508-518.
29.
SakaueSKanaiMTanigawaY, et al.A cross-population atlas of genetic associations for 220 human phenotypes. Nat Genet. 2021;53:1415-1424.
30.
HemaniGZhengJElsworthB, et al.The MR-Base platform supports systematic causal inference across the human phenome. eLife. 2018;7:e34408.
31.
SandersonESpillerWBowdenJ. Testing and correcting for weak and pleiotropic instruments in two‐sample multivariable Mendelian randomization. Stat Med. 2021;40:5434-5452.
32.
YavorskaOOBurgessS. MendelianRandomization: an R package for performing Mendelian randomization analyses using summarized data. Int J Epidemiol. 2017;46:1734-1739.
33.
VerbanckMChenC-YNealeBDoR. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018;50:693-698.
34.
ThrallGLipGYHCarrollDLaneD. Depression, anxiety, and quality of life in patients with atrial fibrillation. Chest. 2007;132:1259-1264.
35.
RewiukKWiznerBKlich-RączkaA, et al.Atrial fibrillation independently linked with depression in community-dwelling older population. Results from the nationwide PolSenior project. Exp Gerontol. 2018;112:88-91.
36.
AriansenIDammenTAbdelnoorMTveitAGjesdalK. Mental health and sleep in permanent atrial fibrillation patients from the general population. Clin Cardiol. 2011;34:327-331.
37.
TrovatoGMPacePCangemiEMartinesGFTrovatoFMCatalanoD. Gender, lifestyles, illness perception and stress in stable atrial fibrillation. Clin Ter. 2012;163:281-286.
38.
ChithiramohanTParekhJNKronenbergG, et al.Investigating the association between depression and cerebral haemodynamics-A systematic review and meta-analysis. J Affect Disord. 2022;299:144-158.
39.
Sepehri ShamlooADagresNMüssigbrodtA, et al.Atrial fibrillation and cognitive impairment: new insights and future directions. Heart Lung Circ. 2020;29:69-85.
40.
MinjieZZhijuanXXinxinSShanQ. Mediating effect of coping strategy and psychological status between illness perception and quality of life among patients with atrial fibrillation: a cross-sectional study. BMC Cardiovasc Disord. 2024;24(1):504.
41.
AulinJSiegbahnAHijaziZ, et al.Interleukin-6 and C-reactive protein and risk for death and cardiovascular events in patients with atrial fibrillation. Am Heart J. 2015;170:1151-1160.
42.
KensukeISasanoT. Role of inflammation in the pathogenesis of atrial fibrillation: novel insights from basic and clinical studies. Front Physiol. 2022;13:862164.
43.
BeurelEToupsMNemeroffCB. The bidirectional relationship of depression and inflammation: double trouble. Neuron. 2020;107:234-256.
44.
SchnabelRBLarsonMGYamamotoJF, et al.Relation of multiple inflammatory biomarkers to incident atrial fibrillation. Am J Cardiol. 2009;104:92-96.
45.
MaZChenQLiuZLiXZhangHFengX. Genetically predicted inflammatory proteins and the risk of atrial fibrillation: a bidirectional Mendelian randomization study. Front Cardiovasc Med. 2024;11:1375750.
46.
FichtnerSDeisenhoferIKindsmüllerS, et al.Prospective assessment of short- and long-term quality of life after ablation for atrial fibrillation. J Cardiovasc Electrophysiol. 2012;23:121-127.
47.
SangC-HChenKPangX-F, et al.Depression, anxiety, and quality of life after catheter ablation in patients with paroxysmal atrial fibrillation. Clin Cardiol. 2013;36:40-45.
48.
NinniSDombrowiczDde WintherMStaelsBMontaigneD. Nattel S. Genetic factors altering immune responses in atrial fibrillation: JACC review topic of the week. J Am Coll Cardiol. 2024;83(12):1163-1176.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
