Identifying the potential causal role of insomnia symptoms on 11,409 health-related outcomes: a phenome-wide Mendelian randomisation analysis in UK Biobank

Mark J. Gibson*, Deborah A. Lawlor, Louise A.C. Millard

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

6 Citations (Scopus)

Abstract

Background: Insomnia symptoms are widespread in the population and might have effects on many chronic conditions and their risk factors but previous research has focused on select hypothesised associations/effects rather than taking a systematic hypothesis-free approach across many health outcomes. Methods: We performed a Mendelian randomisation (MR) phenome-wide association study (PheWAS) in 336,975 unrelated white-British UK Biobank participants. Self-reported insomnia symptoms were instrumented by a genetic risk score (GRS) created from 129 single-nucleotide polymorphisms (SNPs). A total of 11,409 outcomes from UK Biobank were extracted and processed by an automated pipeline (PHESANT) for the MR-PheWAS. Potential causal effects (those passing a Bonferroni-corrected significance threshold) were followed up with two-sample MR in MR-Base, where possible. Results: Four hundred thirty-seven potential causal effects of insomnia symptoms were observed for a diverse range of outcomes, including anxiety, depression, pain, body composition, respiratory, musculoskeletal and cardiovascular traits. We were able to undertake two-sample MR for 71 of these 437 and found evidence of causal effects (with directionally concordant effect estimates across main and sensitivity analyses) for 30 of these. These included novel findings (by which we mean not extensively explored in conventional observational studies and not previously explored using MR based on a systematic search) of an adverse effect on risk of spondylosis (OR [95%CI] = 1.55 [1.33, 1.81]) and bronchitis (OR [95%CI] = 1.12 [1.03, 1.22]), among others. Conclusions: Insomnia symptoms potentially cause a wide range of adverse health-related outcomes and behaviours. This has implications for developing interventions to prevent and treat a number of diseases in order to reduce multimorbidity and associated polypharmacy.

Original languageEnglish
Article number128
JournalBMC Medicine
Volume21
Issue number1
DOIs
Publication statusPublished - Dec 2023

Bibliographical note

Funding Information:
This work was supported by a Medical Research Council (MRC) PhD studentship to MJG (grant code: MC_UU_00011/7), Diabetes UK (17/0005700), the MRC (MR/V033867/1), and the British Heart Foundation (AA/18/1/34219). DAL is further supported by a British Heart Foundation Chair (CH/F/20/90003) and National Institute of Health Research Senior Investigator award (NF-0616–10102). LACM is supported by a University of Bristol Vice-Chancellor’s fellowship. All three authors work in a unit that is funded by the University of Bristol and Medical Research Council (MC_UU_00011/1, MC_UU_00011/6 and MC_UU_00011/7).

Publisher Copyright:
© 2023, The Author(s).

Keywords

  • Insomnia
  • Mendelian randomisation
  • MR-PheWAS
  • UK Biobank

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