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Evaluation of the Genetics of Hidradenitis Suppurativa

化脓性汗腺炎的遗传学评价

基本信息

批准号：
9979198
负责人：
Yun Li
金额：
$ 16.9万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9979198
关键词：
Adolescence Adolescent Affect African American Age Age of Onset American Basic Science Biological Candidate Disease Gene Characteristics Chronic Clinic Clinical Clinical Data Clinical Trials Counseling Country DNA Data Dermatologic Dermatologist Dermatology Development Disease Disease Progression Ethnic Origin Etiology Evaluation Family Family history of Female Foundations Functional disorder Funding Future General Population Genes Genetic Genetic Predisposition to Disease Genetic Risk Genome Genotype Goals Guidelines Hidradenitis Suppurativa Human Incidence Individual Inflammation Inflammatory Inherited Knowledge Lead Life Measures Mediating Methods Mutation Nature North Carolina Onset of illness Outcome Pain Participant Pathogenesis Pathogenicity Pathway interactions Patients Phenotype Play Population Prevalence Prevention strategy Quality of life Recording of previous events Recurrence Relative Risks Reporting Research Risk Risk Estimate Role Sampling Second Degree Relative Severity of illness Siblings Signal Transduction Specimen Subgroup Symptoms Testing Time Trans-Omics for Precision Medicine Translational Research Universities Validation Variant Woman autoinflammation autoinflammatory base case control chronic inflammatory disease cohort design disorder prevention experience follow-up gamma secretase gene discovery genetic pedigree genetic variant genome sequencing genome wide association study genome-wide multidisciplinary notch protein prospective recruit risk variant screening secondary analysis sex skin disorder therapeutic target treatment response treatment strategy young adult

项目摘要

PROJECT SUMMARY/ABSTRACT Hidradenitis suppurativa (HS) is a chronic, painful, severe, inflammatory skin disease that has a devastating effect on patient quality of life. HS occurs in up to 0.5% of the general population, and the incidence has continued to increase over the last decade. Previous studies characterizing cohorts of HS patients have reported family history in 35-38% of patients, and 57% of our patients report an affected first or second degree relative. While HS affects individuals of all ancestries, it appears to disproportionally affect women and African- Americans (AA). The age of onset that is typically in adolescence/young adulthood (ages 15-25 years old) and symptoms continue throughout much of life. To date, genetic variants that may cause HS have been described in 27 families and 15 sporadic cases, but in follow-up screening studies, pathogenic genetic variants were detected in only 5 of 21 families and 2 of 68 patients with sporadic cases of HS. Genetic variants implicated in autoinflammation, abnormal follicular differentiation, and HS have been reported in four genes, including three genes encoding subunits of the gamma-secretase complex. However, the familial recurrence risk of HS and genetic contributions to HS are poorly understood for most patients. We hypothesize that systematic examination of the genetic contributions to HS will lead to the identification of genes and pathogenic, inflammatory pathways involved in disease onset and progression. In this study, we propose to examine the genetic basis of HS in a new cohort of 700 HS patients. Participants are being recruited from one of the largest HS populations in the country by chair of the North American HS Guidelines Committee who has experience with clinical trials for HS. At the time of re-submission, we have already collected clinical data, family history, and DNA specimens for 561 HS patients, ~50% African American and ~80% female. We aim to recruit at least 700 patients during the R21 funding period. We will characterize the distribution of disease severity and calculate sibling relative risk, as a measure of familial aggregation, and identify differences in risk based on age, sex, and ethnicity. To perform an unbiased search for new genetic variants associated with HS, we will perform a genome-wide association study (GWAS). For this analysis, we will make use of established methods for case-control matching and the extensive genome-wide sequence data available from the Trans-Omics for Precision Medicine (TOPMed) project and Genome Sequencing Project (GSP) to appropriately select controls. Identification of genetic variants that show evidence for association with HS disease status will provide target variants and candidate genes for further validation and biological study to detect new treatments and possibly prevention of disease.

项目总结/文摘