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Meta-Analysis
. 2013 Aug;45(8):907-11.
doi: 10.1038/ng.2686. Epub 2013 Jun 30.

A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci

David A Hinds  1 , George McMahon, Amy K Kiefer, Chuong B Do, Nicholas Eriksson, David M Evans, Beate St Pourcain, Susan M Ring, Joanna L Mountain, Uta Francke, George Davey-Smith, Nicholas J Timpson, Joyce Y Tung
Affiliations
Meta-Analysis

A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci

David A Hinds et al. Nat Genet. 2013 Aug.

Abstract

Allergic disease is very common and carries substantial public-health burdens. We conducted a meta-analysis of genome-wide associations with self-reported cat, dust-mite and pollen allergies in 53,862 individuals. We used generalized estimating equations to model shared and allergy-specific genetic effects. We identified 16 shared susceptibility loci with association P<5×10(-8), including 8 loci previously associated with asthma, as well as 4p14 near TLR1, TLR6 and TLR10 (rs2101521, P=5.3×10(-21)); 6p21.33 near HLA-C and MICA (rs9266772, P=3.2×10(-12)); 5p13.1 near PTGER4 (rs7720838, P=8.2×10(-11)); 2q33.1 in PLCL1 (rs10497813, P=6.1×10(-10)), 3q28 in LPP (rs9860547, P=1.2×10(-9)); 20q13.2 in NFATC2 (rs6021270, P=6.9×10(-9)), 4q27 in ADAD1 (rs17388568, P=3.9×10(-8)); and 14q21.1 near FOXA1 and TTC6 (rs1998359, P=4.8×10(-8)). We identified one locus with substantial evidence of differences in effects across allergies at 6p21.32 in the class II human leukocyte antigen (HLA) region (rs17533090, P=1.7×10(-12)), which was strongly associated with cat allergy. Our study sheds new light on the shared etiology of immune and autoimmune disease.

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Conflict of interest statement

Competing Financial Interests

D.A.H., A.K.K, C.B.D., N.E., J.L.M., U.F., and J.Y.T. are current or former employees of, and own stock or stock options in, 23andMe, Inc.

Figures

Figure 1
Figure 1
Manhattan plot of meta-analysis results for shared effects. The plotted values represent the most-significant scores from the meta-analyses of cat, pollen, and dust mite allergy, with all results with P<10 −4 recomputed using generalized estimating equations to assess effects shared across allergens. Results with P<5×10−8 are shown in red. Gene labels are provided for cross referencing with other results and are not intended to suggest that we have established a causal basis for the observed associations.
Figure 2
Figure 2
Manhattan plot of meta-analysis results for interactions with allergen. Results with P<5×10−8 are shown in red. Interaction tests were performed for markers with P<1e-4 for association with at least one of cat, pollen, or dust mite allergy.
Figure 3
Figure 3
Marginal effect sizes and 95% confidence intervals for rs17533090 for cat, pollen, and dust mite allergy, in the 23andMe and ALSPAC cohorts. Effects are odds ratios for the high risk G allele of rs17533090.
See this image and copyright information in PMC

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