A meta-analysis of genome-wide association studies for serum total IgE in diverse study populations

Levin, Albert M.; Mathias, Rasika A.; Huang, Lirong; Roth, Lindsey A.; Daley, Denise; Myers, Rachel A.; Himes, Blanca E.; Romieu, Isabelle; Yang, Mao; Eng, Celeste; Park, Julie E.; Zoratti, Karla; Gignoux, Christopher R.; Torgerson, Dara G.; Galanter, Joshua; Huntsman, Scott; Nguyen, Elizabeth A.; Becker, Allan B.; Chan‐Yeung, Moira; Kozyrskyj, Anita L.; Kwok, Pui‐Yan; Gilliland, Frank D.; Gauderman, W. James; Bleecker, Eugene R.; Raby, Benjamin A.; Meyers, Deborah A.; London, Stephanie J.; Martínez, Fernando D.; Weiss, Scott T.; Burchard, Esteban G.; Nicolae, Dan L.; Ober, Carole; Barnes, Kathleen C.; Williams, L. Keoki

doi:10.1016/j.jaci.2012.10.002

Cited by 56 publications

(45 citation statements)

References 60 publications

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“…Although this region was already known to contain genes that influence IgE levels, 10, 11, 13 in this study we identified an important role of local genetic ancestry. In addition, our genome-wide significant associations are different from those previously described in GWAS involving European populations 10,11,13 or Asian populations. 14 Moreover, for the first time we implicated variation in HLA-DQA1 in affecting IgE levels.…”

Section: Discussionmentioning

confidence: 70%

“…13,26 African American studies included the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE), the Genetic Research on Asthma in the African Diaspora in African American individuals (GRAAD-AA) and in Afro-Caribbean from Barbados (GRAAD-AC), and the Chicago Asthma Genetics study, Collaborative Studies on the Genetics of Asthma, and Severe Asthma Research Program (CAG/CSGA/SARP). European American studies with measured IgE included the Childhood Asthma Management Program (CAMP), the Childhood Asthma Research and Education Network (CARE), and CAG/CSGA/SARP.…”

Section: Methodsmentioning

confidence: 99%

“…9 Recently, five genome wide association studies (GWAS) have revealed single nucleotide polymorphisms (SNPs) near 12 genes to be associated with IgE levels at a genome-wide significance level, including six genes within the major histocompatibility complex (MHC). 10–13 …”

Section: Introductionmentioning

confidence: 99%

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Genome-wide association study and admixture mapping reveal new loci associated with total IgE levels in Latinos

Pino-Yanes

Gignoux

Galanter

et al. 2015

Journal of Allergy and Clinical Immunology

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Background Immunoglobulin E (IgE) is a key mediator of allergic inflammation and is frequently elevated in allergic disorders. Objective To identify genetic variants associated with IgE levels in Latinos. Methods We performed a genome-wide association study (GWAS) and admixture mapping of total IgE levels in 3,334 Latinos from the Genes-environments & Admixture in Latino Americans (GALA II) study. Replication was evaluated in 454 Latinos, 1,564 European Americans, and 3,187 African Americans from independent studies. Results We confirmed associations of six genes identified by previous GWAS and identified a novel genome-wide significant association of a polymorphism in ZNF365 with total IgE (rs200076616, p=2.3x10−8). We next identified four admixture mapping peaks (6p21.32-p22.1, 13p22-31, 14q23.2, and 22q13.1) where local African, European, and/or Native American ancestry was significantly associated with IgE levels. The most significant peak was 6p21.32-p22.1, where Native American ancestry was associated with lower levels of IgE (p=4.95x10−8). All but 22q13.1 were replicated in an independent sample of Latinos, and two of the peaks were replicated in African Americans (6p21.32-p22.1 and 14q23.2). Fine mapping of 6p21.32-p22.1 identified six genome-wide significant single nucleotide polymorphisms in Latinos, two of which replicated in European Americans. Another SNP was peak-wide significant within 14q23.2 in African Americans (rs1741099, p=3.7x10−6), and replicated in non-African American samples (p=0.011). Conclusion We confirmed genetic associations at six genes, and identified novel associations within ZNF365, HLA-DQA1, and 14q23.2. Our results highlight the importance of studying diverse, multi-ethnic populations to uncover novel loci associated with total IgE levels.

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Section: Discussionmentioning

confidence: 70%

Section: Methodsmentioning

confidence: 99%

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Genome-wide association study and admixture mapping reveal new loci associated with total IgE levels in Latinos

Pino-Yanes

Gignoux

Galanter

et al. 2015

Journal of Allergy and Clinical Immunology

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“…Evidence from several independent genome-wide association studies (GWAS) lend further support to the involvement of HLA-II loci in asthma, allergic sensitisation and increased total IgE level [4][5][6][7][8][9][10][11]. The GABRIEL consortium carried out the largest asthma GWAS to date, by genotyping 10 365 asthma patients and 16 110 controls recruited from 23 studies [4].…”

Section: Introductionmentioning

confidence: 97%

Human leukocyte antigen class II variants and adult-onset asthma: does occupational allergen exposure play a role?

Smit¹,

Strachan²,

Vermeulen³

et al. 2014

Eur Respir J

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Recently, a locus centred on rs9273349 in the HLA-DQ region emerged from genome-wide association studies of adult-onset asthma. We aimed to further investigate the role of human leukocyte antigen (HLA) class II in adult-onset asthma and a possible interaction with occupational exposures.We imputed classical HLA-II alleles from 7579 single-nucleotide polymorphisms in 6025 subjects (1202 with adult-onset asthma) from European cohorts: ECRHS, SAPALDIA, EGEA and B58C, and from surveys of bakers and agricultural workers. Based on an asthma-specific job-exposure matrix, 2629 subjects had ever been exposed to high molecular weight (HMW) allergens. We explored associations between 23 common HLA-II alleles and adult-onset asthma, and tested for gene-environment interaction with occupational exposure to HMW allergens. Interaction was also tested for rs9273349.Marginal associations of classical HLA-II alleles and adult-onset asthma were not statistically significant. Interaction was detected between the DPB1*03:01 allele and exposure to HMW allergens (p50.009), in particular to latex (p50.01). In the unexposed group, the DPB1*03:01 allele was associated with adult-onset asthma (OR 0.67, 95%CI 0.53-0.86). HMW allergen exposures did not modify the association of rs9273349 with adult-onset asthma.Common classical HLA-II alleles were not marginally associated with adult-onset asthma. The association of latex exposure and adult-onset asthma may be modified by DPB1*03:01. @ERSpublicationsIn an analysis involving .6000 European adults, classical HLA-II alleles were not associated with adult-onset asthma

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“…Analysis of data collected within the EVE Consortium revealed ten unique regions associated with serum IgE levels, with the SNP rs9469220 within HLA-DQB1 being most strongly associated. 47 This variant in the MHC locus showed association in all three ethnic groups studied in the EVE Consortium (Caucasian, African American, Latino). A recent report examined both total IgE levels and dust mite-specific IgE in a Korean population.…”

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confidence: 93%

Genome-wide association studies in asthma: progress and pitfalls

March¹,

Sleiman²,

Hákonarson³

2015

AGG

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Genetic studies of asthma have revealed that there is considerable heritability to the phenotype. An extensive history of candidate-gene studies has identified a long list of genes associated with immune function that are potentially involved in asthma pathogenesis. However, many of the results of candidate-gene studies have failed to be replicated, leaving in question the true impact of the implicated biological pathways on asthma. With the advent of genome-wide association studies, geneticists are able to examine the association of hundreds of thousands of genetic markers with a phenotype, allowing the hypothesis-free identification of variants associated with disease. Many such studies examining asthma or related phenotypes have been published, and several themes have begun to emerge regarding the biological pathways underpinning asthma. The results of many genome-wide association studies have currently not been replicated, and the large sample sizes required for this experimental strategy invoke difficulties with sample stratification and phenotypic heterogeneity. Recently, large collaborative groups of researchers have formed consortia focused on asthma, with the goals of sharing material and data and standardizing diagnosis and experimental methods. Additionally, research has begun to focus on genetic variants that affect the response to asthma medications and on the biology that generates the heterogeneity in the asthma phenotype. As this work progresses, it will move asthma patients closer to more specific, personalized medicine.

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A meta-analysis of genome-wide association studies for serum total IgE in diverse study populations

Cited by 56 publications

References 60 publications

Genome-wide association study and admixture mapping reveal new loci associated with total IgE levels in Latinos

Genome-wide association study and admixture mapping reveal new loci associated with total IgE levels in Latinos

Human leukocyte antigen class II variants and adult-onset asthma: does occupational allergen exposure play a role?

Genome-wide association studies in asthma: progress and pitfalls

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