Dataset Information

Multiethnic genome-wide and HLA association study of total serum IgE level.

ABSTRACT:

Background

Total serum IgE (tIgE) is an important intermediate phenotype of allergic disease. Whole genome genetic association studies across ancestries may identify important determinants of IgE.

Objective

We aimed to increase understanding of genetic variants affecting tIgE production across the ancestry and allergic disease spectrum by leveraging data from the National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine program; the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA); and the Atopic Dermatitis Research Network (N = 21,901).

Methods

We performed genome-wide association within strata of study, disease, and ancestry groups, and we combined results via a meta-regression approach that models heterogeneity attributable to ancestry. We also tested for association between HLA alleles called from whole genome sequence data and tIgE, assessing replication of associations in HLA alleles called from genotype array data.

Results

We identified 6 loci at genome-wide significance (P < 5 × 10^-9), including 4 loci previously reported as genome-wide significant for tIgE, as well as new regions in chr11q13.5 and chr15q22.2, which were also identified in prior genome-wide association studies of atopic dermatitis and asthma. In the HLA allele association study, HLA-A∗02:01 was associated with decreased tIgE level (P_discovery = 2 × 10^-4; P_replication = 5 × 10^-4; P_{discovery+replication} = 4 × 10^-7), and HLA-DQB1∗03:02 was strongly associated with decreased tIgE level in Hispanic/Latino ancestry populations (P_{Hispanic/Latino discovery+replication} = 8 × 10^-8).

Conclusion

We performed the largest genome-wide association study and HLA association study of tIgE focused on ancestrally diverse populations and found several known tIgE and allergic disease loci that are relevant in non-European ancestry populations.

SUBMITTER: Daya M

PROVIDER: S-EPMC8665111 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

Multiethnic genome-wide and HLA association study of total serum IgE level.

Daya Michelle M Cox Corey C Acevedo Nathalie N Boorgula Meher P MP Campbell Monica M Chavan Sameer S Cho Michael H MH David Gloria L GL Kachroo Priyadarshini P Lasky-Su Jessica J Li Xingnan X McHugh Caitlin P CP Qiao Dandi D Rafaels Nicholas N Beck Lisa A LA Bleecker Eugene R ER Caraballo Luis L Cupples Adrienne L AL Figueiredo Camila A CA Gallo Richard L RL Hanifin Jon J Hansel Nadia N NN Hata Tissa R TR Hersh Craig P CP Knight-Madden Jennifer J Leung Donald Y M DYM Guttman-Yassky Emma E Meyers Deborah A DA O'Connor George G Ober Carole C Ong Peck Y PY Ortega Victor E VE Paller Amy S AS Putcha Nirupama N Reed Robert M RM Schneider Lynda C LC Silverman Edwin K EK Slifka Mark K MK Spergel Jonathan M JM Vasan Ramachandran S RS Viaud-Martinez Karine A KA Watson Harold H Weiss Scott T ST Ruczinski Ingo I Beaty Terri H TH Mathias Rasika A RA Barnes Kathleen C KC

The Journal of allergy and clinical immunology 20210915 6

<h4>Background</h4>Total serum IgE (tIgE) is an important intermediate phenotype of allergic disease. Whole genome genetic association studies across ancestries may identify important determinants of IgE.<h4>Objective</h4>We aimed to increase understanding of genetic variants affecting tIgE production across the ancestry and allergic disease spectrum by leveraging data from the National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine program; the Consortium on Asthma among Afr ...[more]

PMID: 34536413

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Project description:The global rise in fatty liver is a major public health problem. Thus, it is critical to identify both global and population-specific genetic variants associated with liver fat. We conducted a genome-wide association study (GWAS) of percent liver fat and nonalcoholic fatty liver disease (NAFLD) assessed by magnetic resonance imaging in 1,709 participants from the population-based Multiethnic Cohort Adiposity Phenotype Study. Our participants comprised older adults of five U.S. racial/ethnic groups: African Americans (n = 277), Japanese Americans (n = 424), Latinos (n = 348), Native Hawaiians (n = 274), and European Americans (n = 386). The established missense risk variant rs738409 located in patatin-like phospholipase domain containing 3 (PNPLA3) at 22q13 was confirmed to be associated with percent liver fat (P = 3.52 × 10-15) but more strongly in women than men (P heterogeneity = 0.002). Its frequency correlated with the prevalence of NAFLD across the five ethnic/racial groups. Rs738409 was also associated with homeostasis model assessment of insulin resistance (HOMA-IR) (beta = 0.028; P = 0.009) and circulating levels of insulin (beta = 0.022; P = 0.020) and alanine aminotransferase (beta = 0.016; P = 0.030). A novel association of percent liver fat with rs77249491 (located at 6q13 between limb region 1 domain containing 1 [LMBRD1] and collagen type XIX alpha 1 chain [COL19A1] (P = 1.42 × 10-8) was also observed. Rs7724941 was associated with HOMA-IR (beta = 0.12; P = 0.0005), insulin (beta = 0.11; P = 0.0003), triglycerides (beta = 0.059; P = 0.01), high-density lipoprotein (beta = -0.046; P = 0.04), and sex hormone binding globulin (beta = -0.084; P = 0.0012). This variant was present in Japanese Americans (minor allele frequency [MAF], 8%) and Native Hawaiians (MAF, 2%). Conclusion: We replicated the PNPLA3 rs738409 association in a multiethnic population and identified a novel liver fat risk variant in Japanese Americans and Native Hawaiians. GWASes of percent liver fat in East Asian and Oceanic populations are needed to replicate the rs77249491 association.

Dataset Information

Multiethnic genome-wide and HLA association study of total serum IgE level.

Background

Objective

Methods

Results

Conclusion

Publications

Multiethnic genome-wide and HLA association study of total serum IgE level.

Similar Datasets

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