Benign Ethnic Neutropenia/Leukopenia (BEN) in African-Americans

Benign ethnic neutropenia (BEN) is a clinical condition more commonly observed in African-Americans. It is characterized by a relative reduction in neutrophil count by about 1000 cells per microliter, leading to a decrease in total leukocyte count by similar decrement. Previous reports of this condition showed that there was neither higher frequency nor increased severity of infections in affected individuals. Bone marrow examinations showed normal white cell maturation; and ex vivo culture of marrow cells showed low normal or slightly reduced number of myeloid colonies. Under physiologic stress, the increases in neutrophil and leukocyte counts of BEN individuals are slightly lower, compared to normal African-Americans or Caucasians. These clinical observations suggest that BEN results from a lower 'set point' for cell number in the marrow. Additionally, case reports of familial BEN, the persistence of BEN over many decades in the US, UK, and Africa, and the recent report of Duffy antigen and chemokine receptor (DARC) being associated with neutropenia, all suggest a strong genetic association to neutropenia/leukopenia. Our initial look into microarray analyses in a pilot trial of subjects showed that there were no significant differences in mRNA signals between BEN and normal subjects. Therefore, we are now proposing a larger study, utilizing Illumina Omni Express chips, to look for genetic associations. We have partnered with the Reasons for Geographic and Racial Differences in Stroke study (REGARDS), where nearly half of the cohort are African-Americans. This will be one of the few GWAS being performed in only African-Americans, and will provide valuable genetic information to link with neutropenia and possibly other conditions/diseases. Genotyping was performed by the Johns Hopkins University Center for Inherited Disease Research (CIDR). Quality control of the genotypic and phenotypic data was performed through a collaboration between CIDR and the Genetics Coordinating Center, Department of Biostatistics at the University of Washington, which is funded by a federal contract supported by 14 NIH Institutes (HHSN268200782096C).]]> State Government Data Distribution AgreementCalcvars Data DictionaryCATI Baseline Survey CodebookREGARDS Informed Consent Among REGARDS study participants, African-Americans whose leukocyte counts are in the lowest 1-7th percentile are considered to be 'cases,' or 'leukopenic,' or 'neutropenic.' The controls are African-Americans whose leukocyte counts are in 85-95th percentile.]]> Since our clinical BEN study at NIH do not recruit sufficient number of individuals for GWAS studies, we have partnered with a large national study. The REasons for Geographic and Racial Differences in Stroke (REGARDS) study has already recruited close to 30,000 individuals in the continental US, about half in the southeast US, with half of the participants being African-Americans. DNA samples are available in over 14,000 African-Americans. Clinical parameters, blood samples, and demographic information from these individuals were collected. This is the largest cohort study to date to directly compare with Caucasians. We will be comparing individuals with leukocyte counts at the lowest 1-7th percentile with those at the 85th to 95th percentile. Individuals at either extreme are excluded as they likely represent those with white cell diseases or test result errors.]]>