## 7 Atomic Dermatitis (Eczema)  
AD is a chronic inflammatory skin disease characterised by disturbed skin barrier function and dry, itchy skin. Its prevalence worldwide is increasing and in some countries affects almost 20% of children [106]. Like PV, concordance is observed in twin studies with rates of 0.72-0.86 in monozygotic and 0.21-0.23 in dizygotic twin pairs [107]. A complex interplay between environmental, genetic and immunological factors, as for many common disorders, all contribute to susceptibility and severity. The filaggrin story is central to our understanding of AD and ichthyosis vulgaris (IV). It exemplifies how the study of a monogenic disorder can translate to a complex trait disease. In 2006, null mutations in the filaggrin gene _FLG_ were first identified in Irish families with IV, which often causes dry, scaly skin and is also a strong genetic risk factor for AD [108]. Histological evidence for the possible lack of filaggrin in IV dates back to 1985 [109] however these preliminary studies were hindered by the daunting size and repetitive nature of _FLG_, particularly exon 3. The [PERSON] group developed a successful strategy to analyse this locus with the use of long range PCR to amplify exon 3 in combination with short specific PCRs to amplify remaining overlapping fragments that were then used to reconstruct the repetitive sequence [108]. Further research has identified significant associations of _FLG_ mutations with atopic asthma, allergic rhinitis and peanut allergy [110], as well as early onset and increased severity of AD [111]. These studies have been reproduced in a variety of geographical populations, including European, Japanese, Taiwanese, Chinese, and Korean [112, 113, 114]. Indeed, the correlation between _FLG_ mutations and AD is considered one of the most robust examples of genotype-phenotype relationship in complex trait disease with an odds ratio of up to 13.4 [115]. Filaggrin plays a key role in epidermal barrier function. Briefly, its degradation products act as \"natural moisturising factors\" in the skin and assist the formation of a flattened granular cell layer upon keratinocyte terminal differentiation [116]. Studies describing murine models of filaggrin haploinsufficiency have shown skin barrier impairment and enhanced sensitisation to percutaneous allergens [117, 118]. The significant effect of _FLG_ mutations on AD risk highlights the role of impaired skin barrier function in the pathogenesis of atopic diseases. Filaggrin replacement therapies could prove significant in the management of AD. Recently, [PERSON] _et al_. (2014) [119] identified a novel compound JTC801, with potential therapeutic applicability. This has been shown to increase expression of filaggrin in both human and murine keratinocytes and, when administered orally, it can hinder the development of AD-like inflammation in the NC/nga AD mouse model [119]. Although the AD spotlight has focused largely on filaggrin, several other genes have been implicated in the pathogenesis of this disorder. To date, a total of 19 genome-wide significant (\(p<5\times 10^{-8}\)) susceptibility loci have been identified through GWAS [120]. The first GWAS data was published in 2009 and included 939 cases and 975 controls in addition to 270 complete nuclear families with two affected siblings [121]. It identified a novel susceptibility locus in 11q13.5, located 38 kb downstream of _C11 orf30_. The peak association was observed 68 kb upstream of the leucine rich repeat containing 32 gene (_LRRC32_) which has been shown to be expressed in activated human regulatory T cells [122]. Carriers have a risk of developing AD that is 1.47 times that of controls [121]. A 2011 Meta analysis of GWAS for AD included 5606 cases and 20565 controls and an additional 5419 cases and 19833 controls in a validation study [114]. Three novel risk loci reached genome-wide significance: rs479844 upstream of ovo-like zinc finger 1 (_OVOL1_), rs2164983 near actin-like 9 (_ACTL9_) and rs2897442 in kinesin family member 3A (_KIF3A_).