In-depth haplotype analysis also revealed a protective effect of haplotype HC. Multiple non-coding variants are contained within the HC LD structure; therefore, potential functional variants may indirectly affect receptor function through developmental and/or cell-specific expression of α5, α3 or β4 levels. The risk versus protective effects of HA and HC reinforce an emerging theme in complex genetics that common and rare alleles can display a range of protective, neutral and susceptibility effects [55]. The magnitude of effects reported here (haplotype frequency shifts ∼10%, haplotype-specific odds ratios = 1.5) fall within the range of other common variant effects influencing complex diseases, such as diabetes [56], coronary artery disease [56] [57], psoriasis [58] and inflammatory bowel disease [59]
