Genome and Transcriptome-Wide Association Study of Fibrotic Sarcoidosis in European Americans

Details

• Personal Author:
  Fingerlin TE ; Liao S-Y ; Maier LA ; Fingerlin TE ; Liao S-Y ; Maier LA
• Description:
  Although sarcoidosis may be a relatively benign disease in some, it can result in fibrosis and a generally poor and potentially fatal outcome. Unlike idiopathic pulmonary fibrosis (IPF), which predominantly affects European Americans (EAs) (1), sarcoidosis affects both EAs and African Americans (AAs), with AA fibrotic patients with sarcoidosis tending to be younger (2) and having an overall worse prognosis (3). The differential outcomes in fibrotic sarcoidosis by race may imply differential pathogenesis and/or genetic predisposition by ancestry, as noted in the article by Garman and colleagues (4), who found variants in PVT1 associated with pulmonary fibrosis in AA sarcoidosis. Theirs is an important study highlighting the need for more genetic studies in AAs to understand the potential shared and ancestry-specific genetic risk factors for sarcoidosis and phenotypes such as fibrotic sarcoidosis. The study findings highlight the need to study larger, diverse sarcoidosis populations with specific phenotypes and incorporate other approaches to integrating data from existing studies across diverse populations, some of which are not possible for less-studied populations. These integrative approaches include discovery in a racial/ethnic group with investigation of risk genes/variants in other racial/ethnic groups, investigation of variants identified in similar diseases, and use of integrative omics approaches to define potentially functional variants. As an example, in our large EA genome-wide association study (GWAS), we identified individual variants and HLA alleles associated with sarcoidosis and, in collaboration with colleagues involved in the Garman study, tested whether those variants were associated with sarcoidosis in a large AA GWAS dataset (5). Highlighting these integrative approaches, here we 1) investigate the frequency of a fibrotic sarcoidosis AA risk haplotype reported by Garman and colleagues; 2) perform a discovery GWAS for pulmonary fibrosis in sarcoidosis (instead of investigating only the AA risk haplotype) in our EA GWAS population to identify shared or distinct genetic risk factors for fibrotic sarcoidosis between AAs and EAs; 3) test for potential shared genetic risk factors with another fibrosing pulmonary disease, IPF, using a candidate gene approach; and 4) integrate the association findings with transcriptomic data to prioritize genetic targets via a transcriptome-wide association study (TWAS) for variants associated with fibrotic sarcoidosis. [Description provided by NIOSH]
• Subjects:
  Cohort Studies Fibrosis Occupational Health Safety
• Keywords:
  Cohort Studies Genetic Factors Genomics Sarcoidosis
• ISSN:
  1073-449X
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article ; Journal Article
• Place as Subject:
  Colorado ; OSHA Region 3 ; OSHA Region 8 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH) ; National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health ; Workplace Safety & Health
• Location:
  North America ; North America
• Pages in Document:
  334-337
• Volume:
  209
• Issue:
  3
• NIOSHTIC Number:
  nn:20069666
• Citation:
  Am J Respir Crit Care Med 2024 Feb; 209(3):334-337
• Contact Point Address:
  Shu-Yi Liao, M.D., M.P.H., Sc.D, 1400 Jackson Street, Rm G204, Denver, CO 80206
• Email:
  liaos@njhealth.org
• Federal Fiscal Year:
  2024
• NORA Priority Area:
  Construction ; Manufacturing ; Construction ; Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  False
• Start Date:
  20060901
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine
• End Date:
  20260831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7a94d438ac21e8b28d02546d424fbba4ebb7b1aeac866ae9fcccd71a2c94ca898c4ff7f7d89952b1765c4d64c97cb15e12ce2794c2cd5c4090920df9072d8a8f
• Download URL:
  https://stacks.cdc.gov/view/cdc/208048/cdc_208048_DS1.pdf
• File Type:
  [PDF - 874.94 KB ]