Genome-Wide Association Study Identifies Genes for Hair Growth and Patterning are Associated With Pilonidal Disease.
Source: PubMed, NCBI / U.S. National Library of Medicine
Pilonidal sinus disease is a highly morbid condition characterized by the formation of chronic sinus tracts throughout the sacrococcygeal region. Despite its commonality and strong association with family history, no prior investigation of genetic risk factors for pilonidal sinus disease exists. To identify genetic risk factors for pilonidal sinus disease. A genome-wide association study. The United Kingdom Biobank, FinnGen Biobank, and Penn Medicine BioBank. There were 772,072 participants. Genome-wide significant variants ( p < 5 × 10 -8 ) were mapped to genes using physical distance and gene expression in skin. Genetic correlation between pilonidal sinus disease and morphometric, androgen-driven, and hair phenotypes was estimated with linkage disequilibrium score regression. Finally, a genome-first approach to rare predicted deleterious variants in hair shaft genes TCHH , PADI3 , and TGM3 was conducted for association with pilonidal sinus disease via the Penn Medicine BioBank. A genome-wide association study comprising 2835 individuals with pilonidal sinus disease identified 5 genome-wide significant loci, prioritizing HDAC9, TBX15, WARS2, RP11-293M10.1 , PRKAR1B , TWIST1, GPATCH2L, NEK9 , and EIF2B2 , as putative causal genes; several of these genes have known roles in balding and hair patterning. There was a significant correlation between the genetic background of pilonidal sinus disease and the androgen-driven hair traits of male pattern baldness and
Abstract
Pilonidal sinus disease is a highly morbid condition characterized by the formation of chronic sinus tracts throughout the sacrococcygeal region. Despite its commonality and strong association with family history, no prior investigation of genetic risk factors for pilonidal sinus disease exists. To identify genetic risk factors for pilonidal sinus disease. A genome-wide association study. The United Kingdom Biobank, FinnGen Biobank, and Penn Medicine BioBank. There were 772,072 participants. Genome-wide significant variants ( p < 5 × 10 -8 ) were mapped to genes using physical distance and gene expression in skin. Genetic correlation between pilonidal sinus disease and morphometric, androgen-driven, and hair phenotypes was estimated with linkage disequilibrium score regression. Finally, a genome-first approach to rare predicted deleterious variants in hair shaft genes TCHH , PADI3 , and TGM3 was conducted for association with pilonidal sinus disease via the Penn Medicine BioBank. A genome-wide association study comprising 2835 individuals with pilonidal sinus disease identified 5 genome-wide significant loci, prioritizing HDAC9, TBX15, WARS2, RP11-293M10.1 , PRKAR1B , TWIST1, GPATCH2L, NEK9 , and EIF2B2 , as putative causal genes; several of these genes have known roles in balding and hair patterning. There was a significant correlation between the genetic background of pilonidal sinus disease and the androgen-driven hair traits of male pattern baldness and young age at first facial hair. In a candidate analysis of genes associated with syndromic hair disorders, rare coding variants in TCHH , a monogenic cause of uncombable hair syndrome, were associated with increased prevalence of pilonidal sinus disease (OR 4.81 [95% CI, 2.06-11.2]). This study is limited to European ancestry. However, because there is a higher incidence of pilonidal sinus disease in men of European ancestry, this analysis is focused on the at-risk population. Genetic analysis of pilonidal sinus disease identified shared genetic architecture with hair biology and androgen-driven traits. As the first study investigating the genetic basis of pilonidal sinus disease, this provides biological insight into the long-appreciated connection between the disease state, male sex, and hair. See Video abstract. ANTECEDENTES:La enfermedad del seno pilonidal es una condición muy mórbida caracterizada por la formación de tractos sinusales crónicos en toda la región sacrococcígea. A pesar de su frecuencia y su fuerte asociación con los antecedentes familiares, no se han investigado previamente los factores de riesgo genéticos de la enfermedad sinusal pilonidal.OBJETIVO:Identificar factores genéticos de riesgo para la enfermedad del seno pilonidal.DISEÑO:Estudio de asociación de genoma completo.CONJUNTOS:Biobanco del Reino Unido, Biobanco FinnGen y Biobanco PennMedicine.PACIENTES:772.072 participantes.MEDIDA DE RESULTADO PRINCIPAL:Las variantes significativas en todo el genoma (p < 5x10-8) se asignaron a genes utilizando la distancia física y la expresión génica en la piel. La correlación genética entre la enfermedad del seno pilonidal y los fenotipos morfométricos, androgénicos y de cabello se estimó con regresión de puntuación LD. Por último, se realizó una aproximación genómica a variantes deletéreas raras predichas en los genes del tallo piloso TCHH, PADI3 y TGM3 para su asociación con la enfermedad del seno pilonidal a través del Biobanco PennMedicine.RESULTADOS:El estudio de asociación de todo el genoma, que incluyó a 2.835 individuos con enfermedad del seno pilonidal, identificó 5 loci significativos en todo el genoma, dando prioridad a HDAC9, TBX15, WARS2, RP11-293M10.1, PRKAR1B, TWIST1, GPATCH2L, NEK9 y EIF2B2, como genes causales putativos; varios de estos genes tienen funciones conocidas en la calvicie y el patrón del cabello. Se observó una correlación significativa entre los antecedentes genéticos de la enfermedad del seno pilonidal y los de los rasgos calvicie de patrón masculino y edad temprana del primer vello facial impulsados por andrógenos. En un análisis de genes candidatos asociados a trastornos capilares sindrómicos, las variantes raras de codificación en TCHH, una causa monogénica del síndrome capilar incombustible, se asociaron a una mayor prevalencia de la enfermedad del seno pilonidal (OR 4,81 [IC del 5%, 2,06-11,2]).LIMITACIONES:Este estudio se limita a la ascendencia europea. Sin embargo, debido a que hay una mayor incidencia de la enfermedad sinusal pilonidal en los hombres de ascendencia europea, este análisis se centra en la población de riesgo.CONCLUSIÓN:El análisis genético de la enfermedad del seno pilonidal identificó una arquitectura genética compartida con la biología del cabello y los rasgos impulsados por andrógenos. Siendo el primer estudio que investiga las bases genéticas de la enfermedad del seno pilonidal, esto proporciona una visión biológica de la conexión, apreciada desde hace tiempo, entre el estado de la enfermedad, el sexo masculino y el cabello. (Traducción-Dr. Aurian Garcia Gonzalez ).