Characterisation of insomnia as an environmental risk factor for asthma via Mendelian randomization and gene environment interaction

Abstract

Asthma is a complex disease that is reportedly associated with insomnia. However, the causal directionality of this association is still unclear. We used asthma and insomnia-associated single nucleotide polymorphisms (SNPs) and genome-wide association study (GWAS) summary statistics to test the causal directionality between insomnia and asthma via Mendelian randomization (MR) analysis. We also performed a cross-trait meta-analysis using UK Biobank GWAS summary statistics and a gene–environment interaction study using data from UK Biobank. The interaction of genetic risk score for asthma (GRSasthma) with insomnia on asthma was tested by logistic regression. Insomnia was a risk factor for the incidence of asthma, as revealed by three different methods of MR analysis. However, asthma did not act as a risk factor for insomnia. The cross-trait meta-analysis identified 28 genetic loci shared between asthma and insomnia. In the gene–environment interaction study, GRSasthma interacted with insomnia to significantly affect the risk of asthma. The results of this study highlight the importance of insomnia as a risk factor of asthma, and warrant further analysis of the mechanism through which insomnia affects the risk of asthma.

Exploring genetic association of insomnia with allergic disease and asthma: a bidirectional Mendelian randomization study

“…Unfortunately, we could not find evidence that genetically predicted allergic disease, asthma, or moderate-to-severe asthma was causally linked with the increased risk of insomnia. The similar finding was observed by another MR analysis [12]. It seems that not all epidemiological link can be confirmed by MR study.…”

“…Insomnia is highly prevalent among patients with allergic disease, and it is reported that 44% to 70% of asthma patients and 33% to 87% of atopic dermatitis people have symptoms of insomnia [8,9]. And the converse is also true that poor sleep itself could cause or worsen allergic disease [8][9][10][11][12]. Two longitudinal observational studies have provided supportive evidence that insomnia carried an increased risk of newly-onset asthma [8,11].…”

Gene‐environment interactions in childhood asthma revisited; expanding the interaction concept

“…Polygenic risk score (PRS) approaches show an increased potential to detect significant GxE in complex traits compared with methods based on individual SNPs 54,55 . Mendelian Randomization (MR) strategies also promise to provide additional insights into the causality and directionality of GxE, 56 although they have been scarcely applied to evaluate the mechanisms underlying asthma 57 …”

Highlighting the importance of healthy sleep patterns in the risk of adult asthma under the combined effects of genetic susceptibility: a large-scale prospective cohort study of 455 405 participants

“…4 In addition, asthma can also affect sleep duration, sleep quality, napping and daytime sleepiness. [5][6][7][8] However, the association between sleep and asthma may be bidirectional. There could be a possibility that not only can asthma influence sleep quality, but poor sleep itself could also cause or worsen asthma.…”

“…For example, poor sleep quality and obstructive sleep apnoea were reported more commonly in patients with asthma, especially those with severe asthma 4. In addition, asthma can also affect sleep duration, sleep quality, napping and daytime sleepiness 5–8. However, the association between sleep and asthma may be bidirectional.…”