McDonagh AJG, Birch MP, Tazi Ahnini R, Cork MJ, Messenger AG
Department of Dermatology, Royal Hallamshire Hospital, University of Sheffield, UNITED KINGDOM

We have studied the inheritance patterns of alopecia areata (AA) in 857 index cases and family members (281M, 576F). 635 had AA (190M, 455F). A family history of AA was significantly commoner in female (46%) than male (29%) subjects (p=0.00004) and was associated with an earlier median age at onset of AA (p<0.0002). In the parents of index cases, AA was recorded in the mother of 52 individuals and the father of 25. A female preponderance of AA was also noted in the grandparents. The true sex ratio of individuals with AA has long been uncertain owing to potential ascertainment bias in published series. To clarify this, we have now examined the sex ratio of siblings in each family. In our families, 29/149 brothers (19%) and 104/192 sisters (54%) had AA. The sex ratio of the siblings was 1.29 F:M overall but this increased to 3.6 for those with AA (p<0.0001). In the course of this study, we have also examined the occurrence of nail disease and disorders associated with AA including vitiligo, autoimmunity and atopic diseases. A positive family history of AA was strongly associated with nail disease p=0.0016, vitiligo p<0.0001, atopic diseases p<0.0001 and autoimmunity p=0.028. Thyroid disease was no commoner in individuals with AA but showed an earlier median age at onset in this subgroup. As previously reported, diabetes mellitus was less common in individuals with AA than in unaffected family members p=0.0015. We also noticed a trend towards a similar negative pattern of association of psoriasis in AA. The novel evidence we present for a female predominance in alopecia areata and the disease associations we have documented are now being applied in our studies of candidate genes including the autoimmune regulator (AIRE) gene on chromosome 21 and genes of the MHC.