The heritability of polymorphic light eruption

Polymorphic light eruption is classified as an acquired idiopathic photoder matosis, yet it appears to cluster in families, suggesting a possible genet ic component. In this study, we assess the heritability of polymorphic ligh t eruption using the classical twin model. Polymorphic light eruption was i nvestigated by a nurse-administered questionnaire in a sample of 420 pairs of adult female twins from St Thomas' Hospital UK Adult Twin Registry, incl uding 119 monozygotic and 301 dizygotic pairs. Probandwise concordance for the presence and absence of disease was calculated and the heritability of polymorphic light eruption assessed by a quantitative genetic model fitting approach using Mr software. The prevalence of polymorphic light eruption w as 21% and 18% in monozygotic and dizygotic twins, respectively. A family h istory of polymorphic light eruption in first-degree relatives (not includi ng the cotwin) was present in 12% of affected twin pairs (where at least on e twin had polymorphic light eruption) compared with 4% of unaffected twin pairs, providing evidence of familial clustering (p < 0.0001). The probandw ise concordance for polymorphic light eruption was higher in monozygotic (0 .72) than in dizygotic twin pairs (0.30), indicating a strong genetic effec t. Quantitative genetic modeling found that a model comprising additive gen etic (A) and unique environmental (E) factors provided the most parsimoniou s fit, although a dominant gene effect could also explain our data. In the AE model, 84% (95% confidence interval 65-94%) of the variance in susceptib ility to polymorphic light eruption is attributed to additive genetic facto rs with the remaining 16% (95% confidence interval 6-35%) to unique environ mental effects. These data establish a clear genetic influence in the expre ssion of polymorphic light eruption and provide a basis for examining candi date genes that may be pathogenic in this common condition.