Genome-Wide Interaction Study of Late-Onset Asthma With Seven Environmental Factors Using a Structured Linear Mixed Model in Europeans

Abstract

Asthma is among the most common chronic diseases worldwide, creating a substantial healthcare burden. In late-onset asthma, there are wide global differences in asthma prevalence and low genetic heritability. It has been suggested as evidence for genetic susceptibility to asthma triggered by exposure to multiple environmental factors. Very few genome-wide interaction studies have identified gene-environment (G×E) interaction loci for asthma in adults. We evaluated genetic loci for late-onset asthma showing G×E interactions with multiple environmental factors, including alcohol intake, body mass index, insomnia, physical activity, mental status, sedentary behavior, and socioeconomic status. In gene-by-single environment interactions, we found no genome-wide significant single-nucleotide polymorphisms. However, in the gene-by-multi-environment interaction study, we identified three novel and genome-wide significant single-nucleotide polymorphisms: rs117996675, rs345749, and rs17704680. Bayes factor analysis suggested that for rs117996675 and rs17704680, body mass index is the most relevant environmental factor; for rs345749, insomnia and alcohol intake frequency are the most relevant factors in the G×E interactions of late-onset asthma. Functional annotations implicate the role of these three novel loci in regulating the immune system. In addition, the annotation for rs117996675 supports the body mass index as the most relevant environmental factor, as evidenced by the Bayes factor value. Our findings help to understand the role of the immune system in asthma and the role of environmental factors in late-onset asthma through G×E interactions. Ultimately, the enhanced understanding of asthma would contribute to better precision treatment depending on personal genetic and environmental information.

Development of network‐guided transcriptomic risk score for disease prediction

“…It is furthed identified that SIK2 and SIK3 play essential roles in producing inflammatory mediators that trigger airway inflammation, suggesting inhibitors of these protein kinases may have therapeutic potential for the treatment of mast cell‐driven diseases, such as asthma (Darling et al, 2021). Other RRS genes including CPS1, HSPA7, TXNL4B and PARD6A have also been shown to be linked with asthma (Baek et al, 2022; Shevchenko et al, 2020; Tougan et al, 2008). We would like to point out that the current manuscript can be viewed as an extension to our previous work (Cao et al, 2022), which focused solely on the development of RNA‐seq risk score.…”

Genome-wide associated variants of subclinical atherosclerosis among young people with HIV and gene-environment interactions

“…We further performed age-specific stratified analyses both in PWH and HIV-negative counterparts. The genome-wide significance threshold was considered at P value less than 5 × 10 -8 , and P value less than 1 × 10 -6 indicated a suggestive significance threshold [27,28]. Plots of representative SNPs were generated using LocusZoom online software [29].…”