Allergy-specific Phenome-Wide Association Study for Immunogenes in Turkish Children

Karaca, Sefayet; Civelek, Ersoy; Karaca, Mehmet; Şahiner, Ümit Murat; Özgül, Rıza Köksal; Kocabaş, Can Naci; Polimanti, Renato; Şekerel, Bülent Enis

doi:10.1038/srep33152

Cited by 14 publications

(16 citation statements)

References 41 publications

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“…sCD14 has been suggested to be an important immune modulator for intestinal homeostasis and may play an important role in the infant’s intestinal defense [ 190 ]. Moreover, this protein has been associated with lower risk for asthma in early childhood [ 191 ].…”

Section: Role Of Breast Milk On Microbiota and Immunity Maturationmentioning

confidence: 99%

“…Certain glycosylated proteins, such as strongly glycosylated BM mucins, can interfere with bacterial and viral adherence to the gut epithelium. Mucin-1 (MUC1) is the predominant mucin in BM, present in the surface of fat globules, and inhibits the binding of pathogens to the mucosal epithelia [ 191 ], including pathogenic bacteria, such as H. pylori and rotavirus, which represent the main cause of acute gastrointestinal infectious in infants [ 192 ].…”

Section: Role Of Breast Milk On Microbiota and Immunity Maturationmentioning

confidence: 99%

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Gut Microbiota and Mucosal Immunity in the Neonate

et al. 2018

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Gut microbiota colonization is a complex, dynamic, and step-wise process that is in constant development during the first years of life. This microbial settlement occurs in parallel with the maturation of the immune system, and alterations during this period, due to environmental and host factors, are considered to be potential determinants of health-outcomes later in life. Given that host–microbe interactions are mediated by the immune system response, it is important to understand the close relationship between immunity and the microbiota during birth, lactation, and early infancy. This work summarizes the evidence to date on early gut microbiota colonization, and how it influences the maturation of the infant immune system and health during the first 1000 days of life. This review will also address the influence of perinatal antibiotic intake and the importance of delivery mode and breastfeeding for an appropriate development of gut immunity.

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Section: Role Of Breast Milk On Microbiota and Immunity Maturationmentioning

confidence: 99%

Section: Role Of Breast Milk On Microbiota and Immunity Maturationmentioning

confidence: 99%

Gut Microbiota and Mucosal Immunity in the Neonate

et al. 2018

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“… 5 Phenome-wide association studies (PheWAS) can permit us to detect the full phenotypic spectrum associated with a specific genetic variant and to extricate the possible causal relationships linking the genetic variation to the phenotype of interest. 6 7 …”

Section: Introductionmentioning

confidence: 99%

Phenotypic and Molecular Characterization of Risk Loci Associated With Asthma and Lung Function

Karaca

Atçeken

Karaca

et al. 2020

Allergy Asthma Immunol Res

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Purpose Respiratory diseases have a highly multifactorial etiology where different mechanisms contribute to the individual's susceptibility. We conducted a deep characterization of loci associated with asthma and lung function by previous genome-wide association studies (GWAS). Methods Sixteen variants were selected from previous GWAS of childhood/adult asthma and pulmonary function tests. We conducted a phenome-wide association study of these loci in 4,083 traits assessed in the UK Biobank (n = 361,194 participants). Data from the Genotype-Tissue Expression (GTEx) project were used to conduct a transcriptomic analysis with respect to tissues relevant for asthma pathogenesis. A pediatric cohort assessed with the International Study of Asthma and Allergies in Children (ISAAC) Phase II tools was used to further explore the association of these variants with 116 traits related to asthma comorbidities. Results Our phenome-wide association studies (PheWAS) identified 206 phenotypic associations with respect to the 16 variants identified. In addition to the replication of the phenotypes tested in the discovery GWAS, we observed novel associations related to blood levels of immune cells (eosinophils, neutrophils, monocytes, and lymphocytes) for the asthma-related variants. Conversely, the lung-function variants were associated with phenotypes related to body fat mass. In the ISAAC-assessed cohort, we observed that risk alleles associated with increased fat mass can exacerbate allergic reactions in individuals affected by allergic respiratory diseases. The GTEx-based analysis showed that the variants tested affect the transcriptomic regulation of multiple surrounding genes across several tissues. Conclusions This study generated novel data regarding the genetics of respiratory diseases and their comorbidities, providing a deep characterization of loci associated with asthma and lung function.

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“…Due to its pivotal regulatory role in numerous biological processes, we hypothesize that thyroid function has a broad impact on the human phenome; MR provides an unprecedented opportunity to test this hypothesis. Phenome-wide analysis can permit to discover novel phenotypic relationships of loci previously identified [ 23 , 24 , 25 ]. Therefore, we conducted a phenome-wide Mendelian randomization analysis of thyroid function that investigated 2419 traits in 337,199 individuals from the UK Biobank [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Phenomic Impact of Genetically-Determined Euthyroid Function and Molecular Differences between Thyroid Disorders

Ravera

Carrasco

Polimanti

2018

JCM

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Background: The thyroid plays a key role in development and homeostasis, but it has been difficult to establish causality with diseases and phenotypic traits because of several potential confounders. Methods: To determine the causal effect of euthyroid function, we conducted a two-sample Mendelian randomization study of euthyroid thyrotropin (TSH) and free thyroxine (FT4) levels with respect to 2419 traits assessed in 337,199 individuals from UK Biobank. Additionally, we investigated the molecular differences between hypothyroidism and hyperthyroidism using genome-wide data. Results: After multiple testing correction, sixteen traits appear to be affected by genetically-determined euthyroid TSH, including multiple thyroid-related traits, e.g., hypothyroidism (p = 2.39 × 10−17), height (p = 2.76 × 10−10), body fat distribution (impedance of whole body, p = 4.43 × 10−8), pulse rate (p = 2.84 × 10−8), female infertility (p = 4.91 × 10−6), and hearing aid use (p = 7.10 × 10−5). Moreover, we found a consistent genetic correlation between hypothyroidism and hyperthyroidism (rg = 0.45, p = 5.45 × 10−6) with several immune pathways shared between these diseases. Two molecular pathways survived multiple testing correction for specificity to hyperthyroidism, JAK/STAT signaling (p = 1.02 × 10−6) and Rac guanyl-nucleotide exchange factor activity (p = 4.39 × 10−6). Conclusion: Our data shed new light on the inter-individual variability of euthyroid function and the molecular mechanisms of the two thyroid disorders investigated.

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Allergy-specific Phenome-Wide Association Study for Immunogenes in Turkish Children

Cited by 14 publications

References 41 publications

Gut Microbiota and Mucosal Immunity in the Neonate

Gut Microbiota and Mucosal Immunity in the Neonate

Phenotypic and Molecular Characterization of Risk Loci Associated With Asthma and Lung Function

Phenomic Impact of Genetically-Determined Euthyroid Function and Molecular Differences between Thyroid Disorders

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