A Large Scale Genome Wide Association Study of Asthma in the 23andMe Cohort. D. Hinds, C. Tian, A. K. Kiefer, J. L. Mountain, N. Eriksson, J. Y. Tung 23andMe, Inc., Mountain View, CA.
Asthma and allergic disease are common, chronic conditions with substantial public health burdens. We carried out a genome-wide association study of self-reported asthma in the 23andMe participant cohort, including more than 17,000 cases and 87,000 controls with European ancestry, imputed against 1000 Genomes reference haplotypes. In addition to replicating established asthma GWAS findings, we see genome-wide-significant associations with several loci that have been associated with other forms of atopic disease, including rs17673553 in CLEC16A, rs12542017 near ZBTB10, and rs3001426 near STAT6. Using conditional logistic regression, we see evidence for multiple independent associations at the IL1RL1 locus on chromosome 2, the TSLP locus on chromosome 5, and the IL33 locus on chromosome 9.
We find novel associations with rs2070902 in FCER1G, encoding the gamma subunit of the high affinity IgE receptor; with rs4707609 in BACH2, or basic leucine zipper transcription factor 2; and with rs62192043 near D2HGDH, or mitochondrial D-2-hydroxyglutarate dehydrogenase, and GAL3ST2, or galactose-3-O-sulfotransferase. Variation in BACH2 has previously been associated with a variety of autoimmune diseases. GAL3ST2 is expressed in goblet cells and is involved in production of sulfated mucins. We also find evidence of associations in or near several genes associated with allergies in the 23andMe cohort, including ID2, LPP, TLR1, and PTGER4.
Most genetic associations with asthma and allergy are shared, with similar effect sizes, and identifying risk factors that distinguish between different allergic disease types seems more challenging. We further explore this issue with analyses of the susceptibility loci stratified by disease subgroups, determined by age of onset, triggers, and severity, and with patterns of allergy symptoms.
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