Amber Dahlin, John Ziniti, Carlos Iribarren, Kelan Tantisira, Scott T Weiss1 and Ann Chen Wu
Harvard Medical School, USA
Kaiser Permanente Division of Research, USA
Posters & Accepted Abstracts: J Mol Genet Med
Asthma, a genetically heterogeneous disease, affects over 300 million persons globally and susceptibility to asthma is influenced by environmental and genetic risk factors. Identifying the genetic variants associated with asthma through well powered genome wide association studies (GWAS) in large populations is needed to elucidate the genetic basis of asthma. We conducted a GWAS in 16,272 patients with asthma and 38,269 unaffected controls from the Kaiser Permanente Northern California├ó┬?┬?s (KPNC) Genetic Epidemiology Research on Adult Health and Aging (GERA), one of the largest real-life asthmatic populations. Genomic DNA was extracted from saliva samples and used to generate over 675,000 genetic markers by Affymetrix Axiom arrays and genotypes for six million common variants were imputed using the 1000 Genomes Project as the reference. The mean age of the population was 60.6 years and 63.5% were female. We identified 15 genes associated with asthma at a genome-wide significance level of 5├?┬?10-08 that were discovered in prior GWA studies, including IL33, IL1RL1, WDR36, TSLP, HLA-DQ1, HLA-DQB1, HLA-DRB1, HLA-DRB4, ORMDL3, ZPBP2, GSDMB, MICB, SMAD3, IKZF3 and LRRC3C. In addition, we also identified eight novel significant associations: PTPRC, HLA-DRB3, HLA-DRB5, HLA-DRB6, PORS1C3, LOC105371988, SNU13 and MEI1. The strongest associations were found in a region of chromosome 6 containing the HLA-DQA1 locus (6p21.3). The top ranked GWAS SNP, rs9272513, [P=2.2├?┬?10-15; OR=0.89] present within an intron of HLA-DQA1 was not previously reported as associated with asthma. Among the top ten SNPs in this region, a second SNP, rs1047989 [OR=0.90; P=1.3├?┬?10-13] encoded a leucine to methionine substitution at amino acid position 8 of HLA-DQA1 and was also in moderate linkage disequilibrium (r2=0.6) with rs9272513. Replication of these results is ongoing.
Molecular and Genetic Medicine received 3571 citations as per Google Scholar report