Genetic predictors of cervical dysplasia in African American HIV-infected women: ACTG DACS 268.
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.


DESIGN
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.
['Cespedes|Michelle S|MS|', 'Kerns|Sarah L|SL|', 'Holzman|Robert S|RS|', 'McLaren|Paul J|PJ|', 'Ostrer|Harry|H|', 'Aberg|Judith A|JA|']
D000328:Adult D001741:African Americans D016022:Case-Control Studies D005260:Female D020022:Genetic Predisposition to Disease D015894:Genome, Human D055106:Genome-Wide Association Study D060005:Genotyping Techniques D015658:HIV Infections D006801:Humans D016015:Logistic Models D008875:Middle Aged D065006:Papanicolaou Test D020641:Polymorphism, Single Nucleotide D011786:Quality Control D002578:Uterine Cervical Dysplasia D014626:Vaginal Smears
cervical dysplasia GWAS risk markers