Analyses of shared genetic factors between asthma and obesity in children

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:126

Article

Melen, Erik^1,2,3,4  Himes, Blanca E.^1,2,5,6,7  Brehm, John M.^1,2,8  Boutaoui, Nadia^1,2  Klanderman, Barbara J.^1,2  Sylvia, Jody S.^1,2  Lasky-Su, Jessica^1,2 

[1] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Boston, MA 02115 USA

[3] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden

[4] Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden

[5] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA

[6] Childrens Hosp, Informat Program, Boston, MA 02115 USA

[7] Partners Ctr Personalized Genet Med, Boston, MA USA

[8] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA

关键词: Association;    asthma;    body mass index;    children;    genetics;    genome-wide association study;    obesity;    polymorphism;    single nucleotide polymorphism;   

DOI  :  10.1016/j.jaci.2010.06.030

来源: Elsevier

【 摘 要 】

Background: Epidemiologic studies consistently show associations between asthma and obesity. Shared genetics might account for this association. Objective: We sought to identify genetic variants associated with both asthma and obesity. Methods: On the basis of a literature search, we identified genes from (1) genome-wide association studies (GWASs) of body mass index (BMI; n = 17 genes), (2) GWASs of asthma (n = 14), and (3) candidate gene studies of BMI and asthma (n = 7). We used GWAS data from the Childhood Asthma Management Program to analyze associations between single nucleotide polymorphisms (SNPs) in these genes and asthma (n = 359 subjects) and BMI (n = 537). Results: One top BMI GWAS SNP from the literature, rs10938397 near glucosamine-6-phosphate deaminase 2 (GNPDA2), was associated with both BMI (P = 4 x 10(-4)) and asthma (P = .03). Of the top asthma GWAS SNPs and the candidate gene SNPs, none was found to be associated with both BMI and asthma. Gene-based analyses that included all available SNPs in each gene found associations (P < .05) with both phenotypes for several genes: neuronal growth regulator 1 (NEGR1); roundabout, axon guidance receptor, homolog 1 (ROBO1); diacylglycerol kinase, gamma (DGKG); Fas apoptotic inhibitory molecule 2 (FAIM2); fat mass and obesity associated (FTO); and carbohydrate (N-acetylgalactosamine 4-0) sulfotransferase 8 (CHST8) among the BMI GWAS genes; interleukin 1 receptor-like 1/interleukin 18 receptor 1 (IL1RL1/IL18R1), dipeptidyl-peptidase 10 (DPP10), phosphodiesterase 4D (PDE4D), V-myb myeloblastosis viral oncogene homolog (MYB), PDE10A, IL33, and especially protein tyrosine phosphatase, receptor type D (PTPRD) among the asthma GWAS genes; and protein kinase C, alpha (PRKCA) among the BMI and asthma candidate genes. Conclusions: SNPs within several genes showed associations to BMI and asthma at a genetic level, but none of these associations were significant after correction for multiple testing. Our analysis of known candidate genes reveals some evidence for shared genetics between asthma and obesity, but other shared genetic determinants are likely to be identified in novel loci. (J Allergy Clin Immunol 2010;126:631-7.)

【 授权许可】

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