Investigating the causal interplay between sleep traits and risk of acute myocardial infarction: a Mendelian randomization study

Nikhil Arora; Laxmi Bhatta; Eivind Schjelderup Skarpsno; Håvard Dalen; Bjørn Olav Åsvold; Ben Michael Brumpton; Rebecca Claire Richmond; Linn Beate Strand

doi:10.1186/s12916-023-03078-0

Investigating the causal interplay between sleep traits and risk of acute myocardial infarction: a Mendelian randomization study

BMC Med. 2023 Oct 5;21(1):385. doi: 10.1186/s12916-023-03078-0.

Authors

Nikhil Arora^{1

2}, Laxmi Bhatta^{3

4

5}, Eivind Schjelderup Skarpsno^{6

7}, Håvard Dalen^{8

9

10}, Bjørn Olav Åsvold^{3

11

12}, Ben Michael Brumpton^{3

11

13}, Rebecca Claire Richmond^{14

15}, Linn Beate Strand⁶

Affiliations

¹ K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway. nikhil.arora@ntnu.no.
² Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. nikhil.arora@ntnu.no.
³ K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
⁴ Division of Mental Health Care, St. Olavs Hospital, Trondheim, Norway.
⁵ Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
⁶ Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
⁷ Department of Neurology and Clinical Neurophysiology, St. Olavs Hospital, Trondheim, Norway.
⁸ Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
⁹ Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.
¹⁰ Clinic of Cardiology, St. Olavs Hospital, Trondheim, Norway.
¹¹ HUNT Research Centre, Department of Public Health and Nursing, Norwegian University of Science and Technology, Levanger, Norway.
¹² Department of Endocrinology, Clinic of Medicine, St. Olavs Hospital, Trondheim, Norway.
¹³ Department of Medicine, St. Olavs Hospital, Trondheim, Norway.
¹⁴ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
¹⁵ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.

Abstract

Background: Few studies have investigated the joint effects of sleep traits on the risk of acute myocardial infarction (AMI). No previous study has used factorial Mendelian randomization (MR) which may reduce confounding, reverse causation, and measurement error. Thus, it is prudent to study joint effects using robust methods to propose sleep-targeted interventions which lower the risk of AMI.

Methods: The causal interplay between combinations of two sleep traits (including insomnia symptoms, sleep duration, or chronotype) on the risk of AMI was investigated using factorial MR. Genetic risk scores for each sleep trait were dichotomized at their median in UK Biobank (UKBB) and the second survey of the Trøndelag Health Study (HUNT2). A combination of two sleep traits constituting 4 groups were analyzed to estimate the risk of AMI in each group using a 2×2 factorial MR design.

Results: In UKBB, participants with high genetic risk for both insomnia symptoms and short sleep had the highest risk of AMI (hazard ratio (HR) 1.10; 95% confidence interval (CI) 1.03, 1.18), although there was no evidence of interaction (relative excess risk due to interaction (RERI) 0.03; 95% CI -0.07, 0.12). These estimates were less precise in HUNT2 (HR 1.02; 95% CI 0.93, 1.13), possibly due to weak instruments and/or small sample size. Participants with high genetic risk for both a morning chronotype and insomnia symptoms (HR 1.09; 95% CI 1.03, 1.17) and a morning chronotype and short sleep (HR 1.11; 95% CI 1.04, 1.19) had the highest risk of AMI in UKBB, although there was no evidence of interaction (RERI 0.03; 95% CI -0.06, 0.12; and RERI 0.05; 95% CI -0.05, 0.14, respectively). Chronotype was not available in HUNT2.

Conclusions: This study reveals no interaction effects between sleep traits on the risk of AMI, but all combinations of sleep traits increased the risk of AMI except those with long sleep. This indicates that the main effects of sleep traits on AMI are likely to be independent of each other.

Keywords: Chronotype; Insomnia; Mendelian randomization; Myocardial infarction; Sleep duration.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Genome-Wide Association Study
Humans
Mendelian Randomization Analysis
Myocardial Infarction* / epidemiology
Myocardial Infarction* / genetics
Risk Factors
Sleep / genetics
Sleep Initiation and Maintenance Disorders* / complications
Sleep Initiation and Maintenance Disorders* / epidemiology
Sleep Initiation and Maintenance Disorders* / genetics