Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype.
BACKGROUND
To date, no genome-wide association study (GWAS) has considered the combined phenotype of asthma with hay fever. Previous analyses of family data from the Tasmanian Longitudinal Health Study provide evidence that this phenotype has a stronger genetic cause than asthma without hay fever.


OBJECTIVE
We sought to perform a GWAS of asthma with hay fever to identify variants associated with having both diseases.


METHODS
We performed a meta-analysis of GWASs comparing persons with both physician-diagnosed asthma and hay fever (n = 6,685) with persons with neither disease (n = 14,091).


RESULTS
At genome-wide significance, we identified 11 independent variants associated with the risk of having asthma with hay fever, including 2 associations reaching this level of significance with allergic disease for the first time: ZBTB10 (rs7009110; odds ratio [OR], 1.14; P = 4 × 10(-9)) and CLEC16A (rs62026376; OR, 1.17; P = 1 × 10(-8)). The rs62026376:C allele associated with increased asthma with hay fever risk has been found to be associated also with decreased expression of the nearby DEXI gene in monocytes. The 11 variants were associated with the risk of asthma and hay fever separately, but the estimated associations with the individual phenotypes were weaker than with the combined asthma with hay fever phenotype. A variant near LRRC32 was a stronger risk factor for hay fever than for asthma, whereas the reverse was observed for variants in/near GSDMA and TSLP. Single nucleotide polymorphisms with suggestive evidence for association with asthma with hay fever risk included rs41295115 near IL2RA (OR, 1.28; P = 5 × 10(-7)) and rs76043829 in TNS1 (OR, 1.23; P = 2 × 10(-6)).


CONCLUSION
By focusing on the combined phenotype of asthma with hay fever, variants associated with the risk of allergic disease can be identified with greater efficiency.
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D000328:Adult D000483:Alleles D001249:Asthma D005260:Female D005787:Gene Frequency D014644:Genetic Variation D055106:Genome-Wide Association Study D006801:Humans D037181:Lectins, C-Type D015810:Linkage Disequilibrium D008297:Male D008875:Middle Aged D009004:Monosaccharide Transport Proteins D016017:Odds Ratio D010641:Phenotype D020641:Polymorphism, Single Nucleotide D040641:Quantitative Trait Loci D012097:Repressor Proteins D006255:Rhinitis, Allergic, Seasonal D055815:Young Adult
single nucleotide polymorphism Rhinitis atopy bivariate genetic correlation selection