Five prior GWAS of HIV acquisition used other measures of HIV exposure to define HIV- controls including: mother-to-child transmission,[6] recruitment from an STI clinic,[8] recruitment of HIV- sex workers,[9] and hemophiliacs with probable exposure.[10] However, these studies did not further equalize degree of HIV exposure between cases and controls. An exception is Lingappa et al’s study of serodiscordant heterosexual couples,[7] wherein non-seroconverting couples where matched to seroconverting couples on baseline HIV exposure risk based on unprotected sex with HIV+ partner, male uninfected partner uncircumcised, uninfected partner age <25 years, and infected partner plasma viral RNA level. Further, controls for HIV acquisition analyses were selected based on two levels of high HIV exposure scores. The sample sizes for these 5 GWAS were small, ranging from 226 to 1,379 participants. Two other GWAS of HIV acquisition used population controls.[11,12] Although the most recent GWAS used the largest sample size to date (N = 13,851),[12] the vast majority of population controls are unlikely to have been exposed to HIV. Without exposure to the virus, such controls may be minimally informative for studying host
