Analyses of shared genetic factors between asthma and obesity in children

Abstract

Background Epidemiological studies consistently show associations between asthma and obesity. Shared genetics may account for this association. Objective To identify genetic variants associated with both asthma and obesity. Methods Based on a literature search, we identified genes from: 1) Genome-wide association studies (GWAS) of Body Mass Index (BMI) (n=17 genes), 2) GWAS 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 (CAMP) 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 GNPDA2, was associated with both BMI (p=4 × 10−4) and asthma (p=0.03). 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<0.05) with both phenotypes for several genes: NEGR1, ROBO1, DGKG, FAIM2, FTO and CHST8 among the BMI GWAS genes; ILRL1/IL18R1, DPP10, PDE4D, MYB, PDE10A, IL33 and especially PTPRD among the asthma GWAS genes; and PRKCA among the BMI and asthma candidate genes. Conclusions SNPs within several genes showed associations to BMI and asthma at a gene 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.

Genome-wide association study of the plasma triglyceride response to an n-3 polyunsaturated fatty acid supplementation

“…of hematopoiesis and tumorigenesis. Recently, a study showed that rs9494145 in MYB was associated with both asthma and BMI, although associations with BMI were modest and not signifi cant after correction for multiple comparisons ( 27 ). Further, the rs2952724/rs2629715 upstream of the SLIT2 gene, which is known to suppress tumor growth, had a lower frequency in nonresponders compared with responders.…”

What the Genetic Background of Individuals with Asthma and Obesity Can Reveal: Is β2-Adrenergic Receptor Gene Polymorphism Important?

“…One of them included children from the Childhood Asthma Management Program 66 survey, Melén et al study. 67 The authors presumed that shared genetic factors are possibly associated with genes with pleiotropic effects, such as ADRB2, VDR, LEP, PRKCA, and TNFa. However, while genetic analysis did not reveal any association for these genes, together with no association for ADRB2, and with the comorbidity of asthma and obesity, a trend was observed for glucosamine-6-phosphate deaminase-2 (GNPDA2), protein tyrosine phosphatise, receptor type D (PTPRD), and roundabout axon guidance receptor homolog 1 (ROBO1), although further research is likely required.…”

The Association of a Variant in the Cell Cycle Control GeneCCND1and Obesity on the Development of Asthma in the Swiss SAPALDIA Study

“…Twin studies suggest that shared genetic pathways for asthma and obesity may partly explain the observed associations (20). Candidate gene studies and, more recently, genome-wide association studies have identified a large number of genes associated with either of the two conditions, but these genes do not seem to have a substantial impact on both phenotypes simultaneously (21). Candidate genes which seemed to be important for the asthma risk in obese people or for the higher BMI in asthmatics encompass LEP, TNFA, and PRKCA, regions encoding the adipose tissue derived Notes: Regression models were adjusted for age, sex, study area and smoking status.…”