Evaluating genetic susceptibility to Staphylococcus aureus bacteremia in African Americans using admixture mapping.
The incidence of Staphylococcus aureus bacteremia (SAB) is significantly higher in African American (AA) than in European-descended populations. We used admixture mapping (AM) to test the hypothesis that genomic variations with different frequencies in European and African ancestral genomes influence susceptibility to SAB in AAs. A total of 565 adult AAs (390 cases with SAB; 175 age-matched controls) were genotyped for AM analysis. A case-only admixture score and a mixed χ2(1df) score (MIX) to jointly evaluate both single-nucleotide polymorphism (SNP) and admixture association (P<5.00e-08) were computed using MIXSCORE. In addition, a permutation scheme was implemented to derive multiplicity adjusted P-values (genome-wide 0.05 significance threshold: P<9.46e-05). After empirical multiplicity adjustment, one region on chromosome 6 (52 SNPs, P=4.56e-05) in the HLA class II region was found to exhibit a genome-wide statistically significant increase in European ancestry. This region encodes genes involved in HLA-mediated immune response and these results provide additional evidence for genetic variation influencing HLA-mediated immunity, modulating susceptibility to SAB.
Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
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Cyr
Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.|Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA.
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Allen
Duke Center for Genomic and Computational Biology, Durham, NC, USA.
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Du
Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA.
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Ruffin
Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA.
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Adams
Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA.
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Thaden
Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA.
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Maskarinec
Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA.|School of Medicine, National and Kapodistrian University of Athens, Chaidari, Greece.
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Souli
Dr John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA.
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Guo
Dr John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA.
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Dykxhoorn
Dr John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA.
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Scott
Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.|Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA.
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Fowler
D001741:Black or African American / Q000235:genetics*; D016470:Bacteremia / Q000453:epidemiology* / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D020641:Polymorphism, Single Nucleotide; D013203:Staphylococcal Infections / Q000453:epidemiology* / Q000235:genetics*; D013211:Staphylococcus aureus