As a whole, the set of 117 loci is enriched with genes involved in biological functions and pathways that are expected to have an immune-mediated impact on asthma, while pointing to novel candidates (Supplementary data, Table S7). For example, we find enrichment for genes involved in T cell receptor signaling (including CD3E, CD3G, CD8A, LAT and LCP2) and mitochondrial adenosine triphosphate (ATP) synthesis (including ATP5H, ATP5I and ATP5L). These annotations fit intuitively with the regulation of lymphocyte counts. Lymphocyte homeostasis (in particular, T cell homeostasis) is influenced by T cell receptor interactions at multiple stages of T cell development, including thymic selection, naïve T cell homeostasis and T cell response to stimulation (57). In addition, cellular proliferation, a central process of the lymphocyte response to antigen, is energetically taxing, and there is evidence suggesting that the metabolic pathways activated in T cells can influence not only sensitivity to apoptotic signals, but lineage decisions as well (58,59). These functional annotations also potentially fit well with a role for these genes in asthma pathogenesis, as the classical paradigm for asthma involves a
