Reduced Neutrophil Count in People of African Descent Is Due To a Regulatory Variant in the Duffy Antigen Receptor for Chemokines Gene
2009

Duffy Variant and Neutropenia in African Americans

Sample size: 6005 publication 10 minutes Evidence: high

Author Information

Author(s): David Reich, Michael A. Nalls, W. H. Linda Kao, Ermeg L. Akylbekova, Arti Tandon, Nick Patterson, James Mullikin, Wen-Chi Hsueh, Ching-Yu Cheng, Josef Coresh, Eric Boerwinkle, Man Li, Alicja Waliszewska, Julie Neubauer, Rongling Li, Tennille S. Leak, Lynette Ekunwe, Joe C. Files, Cheryl L. Hardy, Joseph M. Zmuda, Herman A. Taylor, Elad Ziv, Tamara B. Harris, James G. Wilson

Primary Institution: Harvard Medical School

Hypothesis

Is there a specific genetic change responsible for the low white blood cell count in people of African descent?

Conclusion

The study identifies the Duffy Null polymorphism as a significant factor contributing to low neutrophil counts in African Americans.

Supporting Evidence

  • Low neutrophil count is predominantly responsible for low white blood cell count in African Americans.
  • The Duffy Null polymorphism is highly differentiated in frequency between West Africans and European Americans.
  • Carrier status for the European-type allele predicts a significant variance in neutrophil count.
  • Neutrophil count was more strongly associated with the Duffy variant than with ancestry.
  • Individuals homozygous for the null allele have distinctly lower neutrophil counts.
  • Genetic variation at the chromosome 1 locus accounts for the epidemiological difference in neutrophil counts.
  • The study highlights the importance of genetic factors in understanding ethnic differences in immune response.
  • Further investigation is needed to understand the biological mechanisms behind the Duffy variant's effects.

Takeaway

Some African Americans have lower white blood cell counts than people of European descent because of a specific gene variant that affects their immune cells.

Methodology

The study used admixture mapping and analyzed genotype and phenotype data from three large cohort studies.

Potential Biases

Potential bias due to the reliance on self-identified ancestry and the specific cohorts studied.

Limitations

The study primarily focused on African Americans and may not generalize to other populations.

Participant Demographics

Participants were African Americans from the Jackson Heart Study, Health ABC Study, and ARIC Study.

Statistical Information

P-Value

3.8×10−5

Confidence Interval

91% differentiation in allele frequency between populations

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pgen.1000360

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