Identification of Four Novel Loci in Asthma in European American and African American Populations

Almoguera, Berta; Vazquez, Lyam; Mentch, Frank; Connolly, John J.; Pacheco, Jennifer A.; Sundaresan, Agnes S.; Peissig, Peggy L.; Linneman, James G.; McCarty, Catherine A.; Crosslin, David R.; Carrell, David; Lingren, Todd; Namjou‐Khales, Bahram; Harley, John B.; Larson, Eric B.; Jarvik, Gail P.; Brilliant, Murray H.; Williams, Marc S.; Kullo, Iftikhar J.; Hysinger, Erik B.; Sleiman, Patrick; Hákonarson, Hákon

doi:10.1164/rccm.201604-0861oc

Cited by 83 publications

(67 citation statements)

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“…A 2017 study found a further four novel loci after a meta‐analysis on 21 644 European American and African American individuals . 6p21.31, 9p21.2 and 10q21.3 were the loci identified in the European American population with TEK at the 9p21.2 locus of specific interest due to its known involvement in remodelling in the lung .…”

Section: Methods For Studying Genetics Of Respiratory Diseasementioning

confidence: 99%

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Genetic risk factors for the development of pulmonary disease identified by genome‐wide association

Hall

Sayers

2018

Respirology

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Chronic respiratory diseases are a major cause of morbidity and mortality. Asthma and chronic obstructive pulmonary disease (COPD) combined affect over 500 million people worldwide. While environmental factors are important in disease progression, asthma and COPD have long been known to be heritable with genetic components playing an important role in the risk of developing disease. Identification of genetic variation contributing to disease progression is important for a number of reasons including identification of risk alleles, understanding underlying disease mechanisms and development of novel therapies. Genome‐wide association studies (GWAS) have been successful in identifying many loci associated with lung function, COPD and asthma. In recent years, meta‐analyses and improved imputation have facilitated the growth of GWAS in terms of numbers of subjects and the number of single nucleotide polymorphisms (SNP) that can be interrogated. As a consequence, there has been a significant increase in the number of signals associated with asthma, COPD and lung function. SNP that have shown association with lung function reassuringly show a significant overlap with SNP associated with COPD giving a glimpse at pathways that may be involved in COPD mechanisms including genes in, for example, developmental pathways. In asthma, association signals are often in or near genes involved in both adaptive and innate immune response pathways, epithelial cell homeostasis and airway structural changes. The challenges now are translating these genetic signals into a new understanding of lung biology, understanding how variants impact health and disease and how they may provide opportunities for therapeutic intervention.

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Section: Methods For Studying Genetics Of Respiratory Diseasementioning

confidence: 99%

“…6p21.31, 9p21.2 and 10q21.3 were the loci identified in the European American population with TEK at the 9p21.2 locus of specific interest due to its known involvement in remodelling in the lung . In the African American population, PTGES on 9q34.11 was identified as a novel locus …”

Section: Methods For Studying Genetics Of Respiratory Diseasementioning

confidence: 99%

Genetic risk factors for the development of pulmonary disease identified by genome‐wide association

Hall

Sayers

2018

Respirology

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“…Novel initiatives, such as the Pharmacogenomics in Childhood Asthma (PiCA) consortium [65] are emerging and might identify new pharmacogenomics markers in asthma by conducting GWAS meta-analyses. In addition, electronic medical records are becoming increasingly available for research purposes, and might be valuable tools for large genomics studies [66]. An important next step is to link loci identified in GWAS to genes and biological pathways.…”

Section: Expert Commentarymentioning

confidence: 99%

Treatment response heterogeneity in asthma: the role of genetic variation

Vijverberg

Farzan

Slob

et al. 2017

Expert Review of Respiratory Medicine

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Introduction: Asthmatic patients show a large heterogeneity in response to asthma medication. Rapidly evolving genotyping technologies have led to the identification of various genetic variants associated with treatment outcomes. Areas covered: This review focuses on the current knowledge of genetic variants influencing treatment response to the most commonly used asthma medicines: short-and long-acting beta-2 agonists (SABA/ LABA), inhaled corticosteroids (ICS) and leukotriene modifiers. This review shows that various genetic variants have been identified, but none are currently used to guide asthma treatment. One of the most promising genetic variants is the Arg16 variant in the ADRB2 gene to guide LABA treatment in asthmatic children. Expert commentary: Poor replication of initially promising results and the low fraction of variability accounted for by single genetic variants inhibit pharmacogenetic findings to reach the asthma clinic. Nevertheless, the identification of genetic variation influencing treatment response does provide more insights in the complex processes underlying response and might identify novel targets for treatment. There is a need to report measures of clinical validity, to perform precision-medicine guided trials, as well as to understand how genetic variation interacts with environmental factors. In addition, systems biology approaches might be able to show a more complete picture of these complex interactions.ARTICLE HISTORY

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“…The etiology of asthma remains unclear. Asthma is a complicated and polygenic inheritance disease; familial aggregation and genetic predisposition are significant peculiarities of asthma . Thus, the use of molecular genetic methods to explore the etiology and pathogenesis of asthma has become a research hotspot worldwide.…”

Section: Introductionmentioning

confidence: 99%

“…Asthma is a complicated and polygenic inheritance disease; familial aggregation and genetic predisposition are significant peculiarities of asthma. [2][3][4][5] Thus, the use of molecular genetic methods to explore the etiology and pathogenesis of asthma has become a research hotspot worldwide. Given the development of human genome haplotype plan data, the reduction in the costs of genome-wide single nucleotide polymorphism (SNP) typing chip, and the emergence of new statistical methods and software, genome-wide association study (GWAS) opens a new chapter in determining the genetic factors of complex diseases.…”

Section: Introductionmentioning

confidence: 99%

Association of GWAS‐supported noncoding area loci rs404860, rs3117098, and rs7775228 with asthma in Chinese Zhuang population

Liang

Deng

Wei

et al. 2019

Clinical Laboratory Analysis

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Background Asthma is a complicated and polygenic inheritance disease, and its prevalence increases worldwide. Recent genome‐wide association studies (GWASs) identified a significant association of single nucleotide polymorphism with asthma in the Japanese population. This study aimed to examine the association of GWAS‐supported noncoding area loci, namely rs404860, rs3117098, and rs7775228, with asthma in Chinese Zhuang population. Methods A case‐control study involving 223 individuals, comprising 123 patients with asthma and 100 healthy controls, was conducted. Genotypes were determined by polymerase chain reaction (PCR)/ligase detection reaction assay. The association between gene polymorphisms and asthma risk was calculated by logistic regression analysis using different genetic models through comparisons of alleles (A vs a), homozygote genotypes (AA vs aa), heterozygote genotypes (Aa vs aa), dominant models (AA+Aa vs aa), and recessive models (AA vs. Aa+aa). Results The distribution of the genotype frequency of rs3117098 was statistically different between the case and control groups. For rs3117098, significant associations were observed through comparisons of alleles (OR: 1.832, 95% CI: 1.048‐3.204, P = .034) and dominant models (OR: 2.065, 95% CI: 1.001‐4.260, P = .050). The statistical analysis showed no significant difference for loci rs404860 and rs7775228 between patients with asthma and controls. Conclusion rs3117098 may be the risk factor for asthma in Chinese Zhuang population.

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Identification of Four Novel Loci in Asthma in European American and African American Populations

Abstract: This study adds to understanding of the genetic architecture of asthma in European Americans and African Americans and reinforces the need to study populations of diverse ethnic backgrounds to identify shared and unique genetic predictors of asthma.

Cited by 83 publications

References 46 publications

Genetic risk factors for the development of pulmonary disease identified by genome‐wide association

Genetic risk factors for the development of pulmonary disease identified by genome‐wide association

Treatment response heterogeneity in asthma: the role of genetic variation

Association of GWAS‐supported noncoding area loci rs404860, rs3117098, and rs7775228 with asthma in Chinese Zhuang population

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