In Vitro Whole-Genome Analysis Identifies a Susceptibility Locus for HIV-1
Figure 2
Genome Scan and Fine Mapping of an HIV-1 Susceptibility Locus, and In Vitro Validation of the Candidate SNP Marker
(A) Linkage analysis with 15 families and 2,600 markers identifies a quantitative trait locus (QTL) on HSA8q24.3. The highest multipoint LOD score of 2.89, p = 1.3 × 10−04 (marker rs1398296) was significant at genome-wide level as determined by permutation analysis (95% significance threshold of 2.83, dotted line).
(B) Association analysis in 56 unrelated individuals, using 521 SNPs from the HapMap project centered 3 Mb around the initial QTL, identifies marker rs2572886 (p = 1.8 × 10−5). The association remained significant after correction for multiple testing by Bonferroni (dashed line) or permutation analysis (dotted line).
(C) The candidate marker is associated with a significant 1.4-fold increase in susceptibility to the HIV.GFP.
(D) rs2572886A is associated with a significant 1.6-fold increase in susceptibility of CD4+ T cells from healthy blood donors to replicating HIV-1, differences between the alleles remain significant (p = 0.0331) after removing the outliers.