BACKGROUND: Male-pattern baldness (androgenetic alopecia, AGA) is the most common form of hair loss among humans. Research has shown that it is caused by genetic factors. Numerous studies have unequivocally identified two major genetic risk loci for AGA: the X-chromosomal AR/EDA2R locus, and the PAX1/FOXA2 locus on chromosome 20. OBJECTIVES: To identify further candidate genes for AGA, and thus gain further insights into this phenotype. METHODS: A German sample of 581 severely affected cases and 617 controls was used to perform a genome-wide association study. The identified associated locus was further analysed by fine-mapping, and then independently replicated in an Australian sample. Expression and pathway analyses were performed to characterize the susceptibility gene identified. RESULTS: The most significant association signal was obtained for rs756853 (P = 1·64 × 10(-7) ), which is located intronically in the histone deacetylase 9 (HDAC9) gene. Fine-mapping and a family-based analysis revealed that rs756853 and the 6-kb distal rs2249817 were the most highly associated single nucleotide polymorphisms. The association finding was replicated in an independent Australian sample, when the analysis was restricted to severely affected cases and unaffected controls (P = 0·026). Analysis of rs2249817 in a combined sample of severely affected German and Australian cases and unaffected controls revealed a strong association signal (P = 9·09 × 10(-8) ). Tissue expression studies demonstrated HDAC9 expression in various tissues, including tissues of relevance to AGA. No strong genotypic effects were observed in genotype-specific expression or splice studies. Pathway analyses supported the hypothesis that HDAC9 plays a functional role in AGA via interaction with the AR gene. CONCLUSIONS: The present study suggests that HDAC9 is the third AGA susceptibility gene.
BACKGROUND: Male-pattern baldness (androgenetic alopecia, AGA) is the most common form of hair loss among humans. Research has shown that it is caused by genetic factors. Numerous studies have unequivocally identified two major genetic risk loci for AGA: the X-chromosomal AR/EDA2R locus, and the PAX1/FOXA2 locus on chromosome 20. OBJECTIVES: To identify further candidate genes for AGA, and thus gain further insights into this phenotype. METHODS: A German sample of 581 severely affected cases and 617 controls was used to perform a genome-wide association study. The identified associated locus was further analysed by fine-mapping, and then independently replicated in an Australian sample. Expression and pathway analyses were performed to characterize the susceptibility gene identified. RESULTS: The most significant association signal was obtained for rs756853 (P = 1·64 × 10(-7) ), which is located intronically in the histone deacetylase 9 (HDAC9) gene. Fine-mapping and a family-based analysis revealed that rs756853 and the 6-kb distal rs2249817 were the most highly associated single nucleotide polymorphisms. The association finding was replicated in an independent Australian sample, when the analysis was restricted to severely affected cases and unaffected controls (P = 0·026). Analysis of rs2249817 in a combined sample of severely affected German and Australian cases and unaffected controls revealed a strong association signal (P = 9·09 × 10(-8) ). Tissue expression studies demonstrated HDAC9 expression in various tissues, including tissues of relevance to AGA. No strong genotypic effects were observed in genotype-specific expression or splice studies. Pathway analyses supported the hypothesis that HDAC9 plays a functional role in AGA via interaction with the AR gene. CONCLUSIONS: The present study suggests that HDAC9 is the third AGA susceptibility gene.
Authors: Fan Liu; Merel A Hamer; Stefanie Heilmann; Christine Herold; Susanne Moebus; Albert Hofman; André G Uitterlinden; Markus M Nöthen; Cornelia M van Duijn; Tamar Ec Nijsten; Manfred Kayser Journal: Eur J Hum Genet Date: 2015-10-28 Impact factor: 4.246
Authors: Francesca Lolli; Francesco Pallotti; Alfredo Rossi; Maria C Fortuna; Gemma Caro; Andrea Lenzi; Andrea Sansone; Francesco Lombardo Journal: Endocrine Date: 2017-03-28 Impact factor: 3.633
Authors: Mercedes Lobera; Kevin P Madauss; Denise T Pohlhaus; Quentin G Wright; Mark Trocha; Darby R Schmidt; Erkan Baloglu; Ryan P Trump; Martha S Head; Glenn A Hofmann; Monique Murray-Thompson; Benjamin Schwartz; Subhas Chakravorty; Zining Wu; Palwinder K Mander; Laurens Kruidenier; Robert A Reid; William Burkhart; Brandon J Turunen; James X Rong; Craig Wagner; Mary B Moyer; Carrow Wells; Xuan Hong; John T Moore; Jon D Williams; Dulce Soler; Shomir Ghosh; Michael A Nolan Journal: Nat Chem Biol Date: 2013-03-24 Impact factor: 15.040
Authors: Jessica L Fleming; Amy M Dworkin; Dawn C Allain; Soledad Fernandez; Lai Wei; Sara B Peters; O Hans Iwenofu; Katie Ridd; Boris C Bastian; Amanda Ewart Toland Journal: Int J Cancer Date: 2013-07-16 Impact factor: 7.396