Late Breaking Abstract - Shared genetic origins of obesity and poor ICS response in children with asthma

AbstractBackgroundShort-acting B2-adrenergic receptor agonists (SABAs) are the most commonly prescribed asthma medications worldwide. Response to SABAs is measured as bronchodilator drug response (BDR), which varies among racial/ethnic groups in the U.S 1, 2. However, the genetic variation that contributes to BDR is largely undefined in African Americans with asthma3ObjectiveTo identify genetic variants that may contribute to differences in BDR in African Americans with asthma.MethodsWe performed a genome-wide association study of BDR in 949 African American children with asthma, genotyped with the Axiom World Array 4 (Affymetrix, Santa Clara, CA) followed by imputation using 1000 Genomes phase 3 genotypes. We used linear regression models adjusting for age, sex, body mass index and genetic ancestry to test for an association between BDR and genotype at single nucleotide polymorphisms (SNPs). To increase power and distinguish between shared vs. population-specific associations with BDR in children with asthma, we performed a meta-analysis across 949 African Americans and 1,830 Latinos (Total=2,779). Lastly, we performed genome-wide admixture mapping to identify regions whereby local African or European ancestry is associated with BDR in African Americans. Two additional populations of 416 Latinos and 1,325 African Americans were used to replicate significant associations.ResultsWe identified a population-specific association with an intergenic SNP on chromosome 9q21 that was significantly associated with BDR (rs73650726, p=7.69 × 10−9). A trans-ethnic meta-analysis across African Americans and Latinos identified three additional SNPs within the intron of PRKG1 that were significantly associated with BDR (rs7903366, rs7070958, and rs7081864, p≤5 × 10−8).ConclusionsOur findings indicate that both population specific and shared genetic variation contributes to differences in BDR in minority children with asthma, and that the genetic underpinnings of BDR may differ between racial/ethnic groups.Key messagesA GWAS for BDR in African American children with asthma identified an intergenic population specific variant at 9q21 to be associated with increased bronchodilator drug response (BDR).A meta-analysis of GWAS across African Americans and Latinos identified shared genetic variants at 10q21 in the intron of PRKG1 to be associated with differences in BDR.Further genetic studies need to be performed in diverse populations to identify the full set of genetic variants that contribute to BDR.

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The STOPPA Twin Study Explains the Exhaled Nitric Oxide and Asthma Link by Genetics and Sensitization

Twin Research and Human Genetics ◽

10.1017/thg.2017.35 ◽

2017 ◽

Vol 20 (4) ◽

pp. 330-337

Author(s):

Björn Nordlund ◽

Cecilia Lundholm ◽

Vilhelmina Ullemar ◽

Marianne van Hage ◽

Anne K. Örtqvist ◽

...

Keyword(s):

Nitric Oxide ◽

Inhaled Corticosteroids ◽

Population Based ◽

Exhaled Nitric Oxide ◽

Regression Coefficients ◽

Parental Report ◽

Children With Asthma ◽

Genetic And Environmental Factors ◽

Airborne Allergens ◽

Shared Genetic

Background: The link between asthma and exhaled nitric oxide (FENO) is not completely understood. The aim of this study was to estimate the association between FENO and asthma, taking genetics, sensitization, and inhaled corticosteroids (ICS) into account. Methods: A total of 681 twins (53% monozygotic [MZ] and 47% dizygotic [DZ]) from the population-based STOPPA study (mean age 12.6 years) were recruited and information on FENO (parts per billion), parental report of current asthma, sensitization to airborne allergens (Phadiatop; IgE ≥0.35 kUA/l), and ICS-treatment was collected. We estimated the association between FENO and asthma, sensitization, and ICS in all twins and within pairs (DZ and MZ) to address shared genetic and environmental factors. Linear regression of log-transformed FENO was used and results presented as exponentiated regression coefficients (exp[β]), with 95% confidence interval (CI). Results: We found an association between asthma and FENO in all twins, exp(β) 1.31 [1.11, 1.54]. In within-pairs analysis, the association was stronger within DZ pairs discordant for FENO, exp(β) 1.50 [1.19, 1.89], compared to MZ pairs, exp(β) 1.07 [0.84, 1.37], p = .049. There was no difference in FENO in non-sensitized children with asthma, compared to children with neither asthma nor sensitization, exp(β) 0.89 [0.77, 1.03]. However, increased FENO was associated with sensitization, exp(β) 1.48 [1.30, 1.69], and with sensitization together with asthma, exp(β) 1.98 [1.57, 2.51], in all twins and within DZ pairs discordant for FENO, but not in MZ pairs. The FENO asthma association remained in DZ pairs without regular ICS-treatment. Conclusions: The association between FENO and asthma is explained by genetics and sensitization.

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Missed Chances for Flu Vaccine Noted in Children With Asthma

Pediatric News ◽

10.1016/s0031-398x(06)71369-8 ◽

2006 ◽

Vol 40 (10) ◽

pp. 17

Author(s):

ROBERT FINN

Keyword(s):

Children With Asthma ◽

Flu Vaccine

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Data Watch: Percentage of Children With Asthma on the Rise

Pediatric News ◽

10.1016/s0031-398x(06)70943-2 ◽

2006 ◽

Vol 40 (3) ◽

pp. 39

Keyword(s):

Children With Asthma

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Language in mental retardation: Individual and syndromic differences, and neurogenetic variation 1Based on a keynote presentation at the Third European Conference on Psychological Theory and Research in Mental Retardation, Geneva, September 1st, 2000.

Swiss Journal of Psychology ◽

10.1024//1421-0185.60.3.161 ◽

2001 ◽

Vol 60 (3) ◽

pp. 161-178 ◽

Cited By ~ 23

Author(s):

Jean A. Rondal

Keyword(s):

Mental Retardation ◽

Language Development ◽

Oral Language ◽

Psychological Theory ◽

Genetic Syndromes ◽

Explanatory Variables ◽

Keynote Presentation ◽

Genetic Origins ◽

The Sixties ◽

The Individual

Predominantly non-etiological conceptions have dominated the field of mental retardation (MR) since the discovery of the genetic etiology of Down syndrome (DS) in the sixties. However, contemporary approaches are becoming more etiologically oriented. Important differences across MR syndromes of genetic origin are being documented, particularly in the cognition and language domains, differences not explicable in terms of psychometric level, motivation, or other dimensions. This paper highlights the major difficulties observed in the oral language development of individuals with genetic syndromes of mental retardation. The extent of inter- and within-syndrome variability are evaluated. Possible brain underpinnings of the behavioural differences are envisaged. Cases of atypically favourable language development in MR individuals are also summarized and explanatory variables discussed. It is suggested that differences in brain architectures, originating in neurological development and having genetic origins, may largely explain the syndromic as well as the individual within-syndrome variability documented. Lastly, the major implications of the above points for current debates about modularity and developmental connectionism are spelt out.

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