Androgenetic alopecia (AGA, male-pattern baldness) is the most common form of hair loss in humans, affecting 80% of men by age 80.

-  Its etiologic factors are androgen dependency and genetic predisposition. 

-   Recently, two independent genome-wide association studies identified common SNPs on chromosomes 20p11 associated with AGA, and confirmed the association of the previously implicated AR (androgen receptor) region on Xq11-q12  with genome-wide significance. 

-   However, the presence of at least one susceptibility allele at both loci explained only 13.7% of the variance in AGA, suggesting that more genes are involved in the etiology of this trait. 

-  We recently recruited almost 600 individuals and estimated the incidence and the grade of male pattern baldness (by the Hamilton and Norwood grades). This is part of the THISEAS cohort, a case (acute coronary sndrome) – control study. The prevalence of alopecia in our population was 62%. A significant association between family history of alopecia and appearence of alopecia in men (p<0.001) was observed.

-  In an attempt to identify novel AGA loci, we participated in a worlwide initiative for the study of AGA, the Meta-Analysis for Androgenetic Alopecia Novel Determinants Consortium (MAAN).

-   The current analysis compromised a total of around 4000 cases and 9000 controls (total sample size = 13000) of European ancestry combined data from 8 cohorts.

-  We identified six novel genetic loci and confirmed known loci. 

-  Unexpectedly, the 17q21.31 locus harbored genome-wide significant alleles in the MAPT gene, which have also recently been described to be associated with Parkinson’s disease at a genome-wide significant level. Further other genome-wide significant alleles at 17q21.31 have been demonstrated to be under negative selection pressure and are associated with decreased fertility in Icelandic women having fewer children than non-carriers, while men sharing this haplotype have a trend towards decreased fertility. It is unclear exactly how this inversion influences fertility in Europeans. 

-  Using the top SNPs from these six novel loci and the previously described chromosome 20p11 and AR region, we constructed a genotype score based on the weighted number of susceptibility alleles. Individuals in the highest risk quartile of the genotype risk score had a five-fold increased risk of male pattern baldness  compared to the individuals in the lowest quartile. 

-  In conclusion these results highlight unexpected associations between AGA, Parkinson’s disease and fertility, as well as expand our understanding of the role of the androgen pathway in susceptibility to male pattern baldness.