Asthma and lower airway diseaseA genome-wide association study of asthma hospitalizations in adults
Section snippets
Study population and GWAS of asthma hospitalizations
The UKB is a long-term prospective cohort13 that includes extensive phenotypic data and health care information on 502,530 subjects recruited from across the United Kingdom. Study participants were between 40 and 70 years old at the time of recruitment in 2006-2010, when most completed a baseline visit (some participants had 1 or 2 follow-up visits). We used the UKB data released in March 2019. Of the participants, 94% self-identified as white and 88.3% self-identified as both white and
Results
Table I shows the characteristics of the participants in the UKB. Compared with subjects with asthma but no asthma hospitalizations (controls), those with asthma and at least 1 asthma hospitalization (case patients) were significantly more likely to be female. There were no significant differences in age, smoking status, or BMI between case patients and controls.
In the GWAS conducted in the UKB, a locus on chromosome 6p21.3 was significantly associated with asthma hospitalizations (P < 5 × 10–8
Discussion
In a GWAS conducted in white adults with asthma, the SNP rs56151658 was significantly associated with 1.36 times higher odds of hospitalizations for asthma (a type of SAE requiring more intensive health care). Despite differences in case definition, statistical modeling, age, and ethnicity, as well as smaller sample size, several SNPs in strong LD (r2 ≥ 0.90) with rs56151658 were associated with SAEs (including, but not limited to, hospitalizations) in our replication cohorts of Latinos, in the
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2023, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Another study compared Peruvian children with and without asthma based on indigenous versus Spanish-European ancestry and found that those with native indigenous ancestry had higher IgE levels (associated with the HLADR/DQ region; correlated with risk loci rs3135348) and FEV1 values (correlated with risk loci rs4410198).15 To evaluate genetic risk loci associated with asthma-related hospitalizations, a cohort study assessed White British adults and 2 replication cohorts of Latinx children and adolescents from Hartford, Connecticut, and San Juan, Puerto Rico.16 No associations to previously reported gene loci were identified in their study, but unique single nucleotide polymorphisms associated with higher rates of asthma-related hospitalizations and severe asthma exacerbations were identified.
A genome-wide association study on frequent exacerbation of asthma depending on smoking status
2022, Respiratory MedicineCitation Excerpt :In addition, a GWAS on Latino children and adolescents, which was followed by meta-analysis in Puerto Rican and Dutch youth, showed that rs2253681 on FLJ22447 was associated with severe asthma exacerbation possibly through cis-DNA methylation and expression of KCNJ2-AS1 gene [15]. In other GWAS for British adults, 8 kb upstream region of HLA-DQB1 locus at the chromosome 6p21.3 showed association with the risk of asthma hospitalization [16]. However, these studies did not consider environmental factors such as cigarette smoking.
Differential methylation of genes in the human placenta associated with bisphenol A exposure
2021, Environmental ResearchCitation Excerpt :Further pyrosequencing analysis confirmed that the methylation levels of HLA-DRB6 were higher in the high BPA exposure group than in the low exposure group (Table 4). The HLA-DRB genes encode class II histocompatibility molecules expressed by antigen-presenting cells, and abnormal expression of these genes is associated with inflammatory bowel disease, autism, and cancer (2007; Al et al., 2014; Yan et al., 2021). A recent study using 450K methylation arrays found that DNA methylation in HLA-DRB genes was associated with late-onset Alzheimer's disease (Yu et al., 2015).
The UK Biobank Resource was accessed under application no. 43252. The current analysis, like that in the Hartford–Puerto Rico and EVA-PR studies, was supported by the following grants from the US National Institutes of Health (NIH): HL079966, HL117191, and MD011764 (to J.C.C.), HL138098 (to Q.Y.) and U54MD007587 (to the University of Puerto Rico). The Genes-Environments and Admixture in Latino Americans study was supported by NIH grants HL117004 and HL134589; enrollment was supported by the Sandler Family Foundation, the American Asthma Foundation, the RWJF Amos Medical Faculty Development Program, Harry Wm. and Diana V. Hind Distinguished Professorship in Pharmaceutical Sciences II, and NIH grant ES015794. M.P.Y. was supported by grants SAF2017-83417R awarded by the Spanish Ministry of Economy, Industry, and Competitiveness; the State Research Agency and the European Regional Development Funds from the European Union (MINECO/AEI/FEDER, UE); and grant RYC-2015-17205 awarded by the Ramón y Cajal Program by the Spanish Ministry of Economy, Industry, and Competitiveness. E.H.L. was funded by a fellowship (PRE2018-083837) from the Spanish Ministry of Science, Innovation, and Universities.
Disclosure of potential conflict of interest: J. C. Celedon has received research materials from Pharmavite (vitamin D and placebo capsules) and GSK and Merck (inhaled steroids) to provide medications free of charge to participants in National Institutes of Health–funded studies unrelated to the current work. The rest of the authors declare that they have no relevant conflicts of interest.
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These authors shared first authorship.