We carried out a genome-wide association study in 296 individuals with male-pattern baldness (androgenetic alopecia) and 347 controls. We then investigated the 30 best SNPs in an independent replication sample and found highly significant association for five SNPs on chromosome 20p11 (rs2180439 combined P = 2.7 x 10(-15)). No interaction was detected with the X-chromosomal androgen receptor locus, suggesting that the 20p11 locus has a role in a yet-to-be-identified androgen-independent pathway.

Alopecia areata (AA) is a common dermatological disease, which affects nearly 2% of the general population. Association of AA with atopic disease has been repeatedly reported. Loss-of-function mutations in the filaggrin gene (FLG) may be considered as promising candidates in AA, as they have been observed to be a strong risk factor in atopic dermatitis. The FLG mutations R501X and 2282del4 were genotyped in a large sample of AA patients (n=449) and controls (n=473). Although no significant association was observed in the patient sample overall, FLG mutations were significantly associated with the presence of atopic dermatitis among AA patients. Furthermore, the presence of FLG mutations had a strong impact on the clinical course of AA in comorbid patients. For example, 19 of the 22 mutation carriers among AA patients with atopic dermatitis showed a severe form of the disease (P=0.003; odds ratio (OR)=5.47 (95% confidence interval (CI): 1.59-18.76)). In conclusion, our data suggest that when AA occurs in conjunction with FLG-associated atopic disorder, the clinical presentation of AA may be more severe.

Androgenetic alopecia (AGA, male pattern baldness) is the most common form of hair loss. The origin of AGA is genetic, with the X chromosome located androgen receptor gene (AR) being the only risk gene identified to date. We present the results of a genome-wide linkage study of 95 families and linkage fine mapping of the 3q21-q29, 11q14-q25, 18p11-q23, and 19p13-q13 regions in an extended sample of 125 families of German descent. The locus with strongest evidence for linkage was mapped to 3q26 with a nonparametric linkage (NPL) score of 3.97 (empirical p value = 0.00055). This is the first step toward the identification of new susceptibility genes in AGA, a process which will provide important insights into the molecular and cellular basis of scalp hair loss.

Our results suggest the R620W variant of PTPN22 as a general risk factor in AA with the strongest effect observed among patients with a severe type of AA, a positive family history or an early onset of disease.