Genome‐wide interaction study of early‐life smoking exposure on time‐to‐asthma onset in childhood

Sugier, Pierre‐Emmanuel; Sarnowski, Chloé; Granell, Raquel; Laprise, Catherine; Ege, Markus; Margaritte‐Jeannin, Patricia; Dizier, Marie‐Hélène; Minelli, Cosetta; Moffatt, Miriam F.; Lathrop, Mark; Cookson, William; Henderson, A. John; Mutius, Erika von; Kogevinas, Manolis; Demenais, Florence

doi:10.1111/cea.13476

Cited by 10 publications

(10 citation statements)

References 44 publications

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“…3 Nonetheless, the effects of indoor exposures on the genetic risk of asthma-related traits have also been evaluated. For instance, exposure to house dust mite allergens and molds has been proposed TA B L E 1 Summary of the GxE interaction studies of asthma-related traits published between 2019 and 2022 (2874/5399) Whole genome (Rsq ≥ 0.5, MAF ≥ 1%) [35] to potentially modify the effects of several genes on asthma exacerbations (IL9), airway responsiveness (TGFB1), and childhood-onset asthma (IL4), respectively. 27,28 Although most of the environmental factors have been found to increase the genetic risk to develop asthma, certain exposures, such as a farming environment, have been suggested to provide a protective effect in interaction with TLR6, GRM1, and NOD1 polymorphisms against childhood-onset asthma.…”

Section: Inter Ac Ti Ons B E T Ween G Ene S and The Environmentmentioning

confidence: 99%

“…Furthermore, the association of in utero exposure with genetic variants in asthma has been evaluated 34 . Additionally, Sugier et al 35 carried out one of the few GWIS published to date evaluating the effects of tobacco smoke. Specifically, the significant interaction of four novel loci with exposure to cigarette smoke was revealed to potentially influence the time‐to‐asthma onset in children from European populations 35 (Table 3).…”

Section: Interactions Between Genes and The Environmentmentioning

confidence: 99%

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

Hernandez‐Pacheco

Kere

2022

Pediatric Allergy Immunology

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Investigation of gene‐environment interactions (GxE) may provide important insights into the gene regulatory framework in response to environmental factors of relevance for childhood asthma. Over the years, different methodological strategies have been applied, more recently using genome‐wide approaches. The best example to date is the major asthma locus on the 17q12‐21 chromosome region, viral infections, and airway epithelium processes where recent studies have shed much light on mechanisms in childhood asthma. However, there are challenges with the traditional single variant—single exposure interaction models, as they do not encompass the complexity and cumulative effects of multiple exposures or multiple genetic variants. As such, we need to redefine our traditional GxE thinking, and we propose in this review to expand the GxE concept by also evaluating other omics layers, such as epigenetics, transcriptomics, metabolomics, and proteomics. In addition, host factors such as age, gender, and other exposures are very likely to influence GxE effects and need firmly to be considered in future studies.

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Section: Inter Ac Ti Ons B E T Ween G Ene S and The Environmentmentioning

confidence: 99%

Section: Interactions Between Genes and The Environmentmentioning

confidence: 99%

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

Hernandez‐Pacheco

Kere

2022

Pediatric Allergy Immunology

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“…KLHL1 (Kelch Like Family Member 1) is a protein belonging to a family of actin-organizing proteins which modulates voltage-gated calcium channels expressed primarily in various brain tissues (Perissinotti et al, 2014). In a previous genome-wide analysis, the interaction of KLHL1 locus and early life smoke exposure was found to be associated with the onset of childhood asthma (Sugier et al, 2019). Moreover, it was shown that an increased mutation rate in the KLHL1 gene was associated with lifetime benzo(a) pyrene exposure in patients with air-pollution-related lung cancers (Yu et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population

et al. 2022

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Host genetics, an important contributor to the COVID-19 clinical susceptibility and severity, currently is the focus of multiple genome-wide association studies (GWAS) in populations affected by the pandemic. This is the first study from Serbia that performed a GWAS of COVID-19 outcomes to identify genetic risk markers of disease severity. A group of 128 hospitalized COVID-19 patients from the Serbian population was enrolled in the study. We conducted a GWAS comparing (1) patients with pneumonia (n = 80) against patients without pneumonia (n = 48), and (2) severe (n = 34) against mild disease (n = 48) patients, using a genotyping array followed by imputation of missing genotypes. We have detected a significant signal associated with COVID-19 related pneumonia at locus 13q21.33, with a peak residing upstream of the gene KLHL1 (p = 1.91 × 10−8). Our study also replicated a previously reported COVID-19 risk locus at 3p21.31, identifying lead variants in SACM1L and LZTFL1 genes suggestively associated with pneumonia (p = 7.54 × 10−6) and severe COVID-19 (p = 6.88 × 10−7), respectively. Suggestive association with COVID-19 pneumonia has also been observed at chromosomes 5p15.33 (IRX, NDUFS6, MRPL36, p = 2.81 × 10−6), 5q11.2 (ESM1, p = 6.59 × 10−6), and 9p23 (TYRP1, LURAP1L, p = 8.69 × 10−6). The genes located in or near the risk loci are expressed in neural or lung tissues, and have been previously associated with respiratory diseases such as asthma and COVID-19 or reported as differentially expressed in COVID-19 gene expression profiling studies. Our results revealed novel risk loci for pneumonia and severe COVID-19 disease which could contribute to a better understanding of the COVID-19 host genetics in different populations.

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“…[ 26 ] The harmful effects of tobacco on the respiratory system are fully confirmed by both the spirometry and forced oscillation technique results in an Italian study, [ 27 ] which is a trigger for asthma. The first genome-wide study in 2019 [ 28 ] revealed a significant association between early-life tobacco exposure and asthma. Tobacco releases cytokines and causes the proliferation of airway smooth muscle and inflammatory responses through increasing the Kelch-like1 gene encoding the calc-regulatory protein.…”

Section: The External Microbial Environment In Early Life Is Crucial mentioning

confidence: 99%

Microecology research: a new target for the prevention of asthma

Shi

Lan

et al. 2020

Chinese Medical Journal

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The incidence and prevalence of asthma have increased remarkably in recent years. There are lots of factors contributing to the occurrence and development of asthma. With the improvement of sequencing technology, it has been found that the microbiome plays an important role in the formation of asthma in early life. The roles of the microbial environment and human microbiome in the occurrence and development of asthma have attracted more and more attention. The environmental microbiome influences the occurrence of asthma by shaping the human microbiome. The specific mechanism may be related to the immune regulation of Toll-like receptors and T cells (special Tregs). Intestinal microbiome is formed and changed by regulating diet and lifestyle in early life, which may affect the development and maturation of the pulmonary immune system through the intestinal-pulmonary axis. It is well-recognized that both environmental microbiomes and human microbiomes can influence the onset of asthma. This review aims to summarize the recent advances in the research of microbiome, its relationship with asthma, and the possible mechanism of the microbiome in the occurrence and development of asthma. The research of the microbial environment and human microbiome may provide a new target for the prevention of asthma in children who have high-risk factors to allergy. However, further study of “when and how” to regulate microbiome is still needed.

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Genome‐wide interaction study of early‐life smoking exposure on time‐to‐asthma onset in childhood

Cited by 10 publications

References 44 publications

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

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

Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population

Microecology research: a new target for the prevention of asthma

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