Study
PLCO
(Learn more about this study)
Project ID
PLCO-1978
Initial CDAS Request Approval
Sep 9, 2025
Title
Multiethnic Genome Wide Association Study in Acquired Aplastic Anemia
Summary
Aplastic anemia (AA) is a rare immune-mediated form of bone marrow failure. There are marked geographic differences in the incidence of AA between Western and Asian regions and this is a unique and unexplained feature of this disease; for example the incidence of AA is 8.2 per million in Japan compared to France where it is 1.5. The proposed study is designed to investigate the relationship between specific genomic patterns and susceptibility by genome wide association studies (GWAS). Given the heterogeneity of AA, our hypothesis is that significant genetic loci will be associated with: immune response and regulation pathways; hematopoietic stem cell (HSC) number and function, response to regenerative stress; and drug and chemical metabolic systems. Blood samples from patients with AA from the United States, Europe and Asia will undergo SNP array genotyping. We request the use of PLCO genotypying data to provide control individuals who can be matched to the AA patients based on genetic ancestry.
Aims
• Conduct a large multi-ethnic GWAS to discover novel common alleles underlying AA etiology and determine if frequency of these alleles vary by ancestry.
• Perform association analyses of AA cases with genetic ancestry and array matched controls in at least a 1:3, preferably 1:10 ratio by Asian, South Asian and European Ancestry. PLCO data will be used in this in this portion of the study to provide controls for our diverse AA cohort.
• Meta-analyze ancestry specific GWAS results together and evaluate heterogeneity in effects between populations of different ancestry.
• Investigate the translational potential of SNPs that reach genome-wide significance with pathway analysis, functional assays.
Collaborators
Lisa McReynolds National Cancer Institute, National Institutes of Health
Aubrey Hubbard National Cancer Institute, National Institutes of Health
