title: Genetic predictors of cervical dysplasia in African American HIV-infected women: ACTG DACS 268.
abstract: OBJECTIVE
  To examine genome-wide associations in HIV-infected women with a history of cervical dysplasia compared with HIV-infected women with no history of abnormal Papanicolaou (Pap) tests.
  
  
  METHODS
  Case-control study using data from women analyzed for the HIV Controllers Study and enrolled in HIV treatment-naïve studies in the AIDS Clinical Trials Group (ACTG).
  
  
  METHODS
  Genotyping utilized Illumina HumanHap 650 Y or 1MDuo platforms. After quality control and principal component analysis, ~610,000 significant single nucleotide polymorphisms (SNPs) were tested for association. Threshold for significance was P < 5 × 10(-8) for genome-wide associations.
  
  
  RESULTS
  No significant genomic association was observed between women with low-grade dysplasia and controls. The genome-wide association study (GWAS) analysis between women with high-grade dysplasia or invasive cervical cancer and normal controls identified significant SNPs. In the analyses limited to African American women, 11 SNPs were significantly associated with the development of high-grade dysplasia or cancer after correcting for multiple comparisons. The model using significant SNPs alone had improved accuracy in predicting high-grade dysplasia in African American women compared to the use of clinical data (area under the receiver operating characteristic curve for genetic and clinical model = 0.9 and 0.747, respectively).
  
  
  CONCLUSIONS
  These preliminary data serve as proof of concept that there may be a genetic predisposition to developing high-grade cervical dysplasia in African American HIV-infected women. Given the small sample size, the results need to be validated in a separate cohort.
authors: New York University School of Medicine, New York, New York.
authors: Michelle S
authors: MS
authors: Cespedes
authors: Mount Sinai School of Medicine, New York, New York.
authors: Sarah L
authors: SL
authors: Kerns
authors: New York University School of Medicine, New York, New York.
authors: Robert S
authors: RS
authors: Holzman
authors: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
authors: Paul J
authors: PJ
authors: McLaren
authors: Albert Einstein College of Medicine, Bronx, New York.
authors: Harry
authors: H
authors: Ostrer
authors: New York University School of Medicine, New York, New York.
authors: Judith A
authors: JA
authors: Aberg
mesh_terms: D000328:Adult; D001741:Black or African American; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000592:standards; D060005:Genotyping Techniques / Q000592:standards; D015658:HIV Infections / Q000150:complications* / Q000208:ethnology; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D065006:Papanicolaou Test; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011786:Quality Control; D002578:Uterine Cervical Dysplasia / Q000208:ethnology / Q000235:genetics*; D014626:Vaginal Smears
keywords: GWAS; cervical dysplasia; risk markers