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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 (GRS_asthma) 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, GRS_asthma 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.

SUBMITTER: Kim DJ

PROVIDER: S-EPMC8576024 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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

Kim Dong Jun DJ Ha Tae-Woong TW Jung Hae Un HU Baek Eun Ju EJ Lee Won Jun WJ Kim Han Kyul HK Kang Ji-One JO Won Sungho S Lim Ji Eun JE Oh Bermseok B

Scientific reports 20211108 1

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 i ...[more]

PMID: 34750467

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Project description:ObjectivesExtensive researches highlight the detrimental impact of sleep disorders such as insomnia and insufficient sleep duration on kidney function. However, establishing a clear causal relationship between insomnia, sleep duration, and kidney function remains challenging. This study aims to estimate this relationship using Mendelian randomization (MR).MethodsIndependent genetic variants strongly associated with insomnia (N = 462,341) and sleep duration (N = 460,099) were selected as instrumental variables from corresponding genome-wide association studies (GWAS). Kidney function parameters, including serum creatinine, estimated glomerular filtration rate by cystatin C (eGFRcys), acute renal failure (ARF), chronic renal failure (CRF), kidney injury molecule-1, neutrophil gelatinase associated lipocalin, microalbuminuria, cystatin C, and β2 microglobulin, were derived from GWAS databases. A two-sample MR study was conducted to assess the causal relationship between sleep disorders and kidney function, and multivariable MR was used to identify potential mediators. The inverse-variance weighted was used as the primary estimate.ResultsMR analysis found robust evidence indicating that insomnia and short sleep duration were associated with an increased risk of elevated serum creatinine, regardless of adjusting for obesity. Causal links between sleep duration and eGFRcys or cystatin C were also identified. While genetically predicted insomnia and sleep duration were found to potentially impact ARF, CRF, microalbuminuria, and β2 microglobulin, the p-values in multivariable MR analysis became nonsignificant. No pleiotropy was detected.ConclusionsThis study demonstrates a causal impact of insomnia on the risk of elevated serum creatinine and a positive effect of sleep duration on serum creatinine, eGFRcys, and cystatin C. Our findings also suggest their potential indirect effects on ARF, CRF, microalbuminuria, and β2 microglobulin mediated by obesity.

Dataset Information

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

Publications

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

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