The heritability of polymorphic light eruption

Polymorphic light eruption is classified as an acquired idiopathic photodermatosis, yet it appears to cluster in families, suggesting a possible genetic component. In this study, we assess the heritability of polymorphic light eruption using the classical twin model. Polymorphic light eruption was investigated by a nurse-administered questionnaire in a sample of 420 pairs of adult female twins from St Thomas' Hospital UK Adult Twin Registry, including 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 was 21% and 18% in monozygotic and dizygotic twins, respectively. A family history of polymorphic light eruption in first-degree relatives (not including the cotwin) was present in 12% of affected twin pairs (where at least one twin had polymorphic light eruption) compared with 4% of unaffected twin pairs, providing evidence of familial clustering (p < 0.0001). The probandwise concordance for polymorphic light eruption was higher in monozygotic (0.72) than in dizygotic twin pairs (0.30), indicating a strong genetic effect. Quantitative genetic modeling found that a model comprising additive genetic (A) and unique environmental (E) factors provided the most parsimonious 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 susceptibility to polymorphic light eruption is attributed to additive genetic factors with the remaining 16% (95% confidence interval 6-35%) to unique environmental effects. These data establish a clear genetic influence in the expression of polymorphic light eruption and provide a basis for examining candidate genes that may be pathogenic in this common condition.