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Results: 4

1.
Figure  1. 

Figure 1. . From: Admixture Mapping of an Allele Affecting Interleukin 6 Soluble Receptor and Interleukin 6 Levels.

Admixture scan for loci affecting levels of IL-6 SR. The analysis was performed by comparing the 20% of African Americans with the highest levels (n=114) with the 20% with the lowest levels (n=117) of IL-6 SR. A significant signal was contributed by a peak on chromosome 1 (LOD 4.59). Factor-averaging the LOD scores across the genome (to correct for multiple-hypothesis testing) produced a significant genomewide score of 2.03. We also observed a secondary peak with a LOD score of 3.45 on chromosome 9, but this does not reach our published threshold for suggestiveness.26

David  Reich, et al. Am J Hum Genet. 2007 April;80(4):716-726.
2.
Figure  3. 

Figure 3. . From: Admixture Mapping of an Allele Affecting Interleukin 6 Soluble Receptor and Interleukin 6 Levels.

Immunodetection showing no evidence that the IL-6 SR antibody preferentially binds to D358A. We spotted 10-mer, 11-mer, and 12-mer peptides from the IL-6R protein onto a cellulose array with 384 features and immunodetected with the IL-6 SR monoclonal antibody employed in the ELISA assay to study the subjects in the Health ABC Study. Three potential peptide spots from the 10-mers were detected, including an intense positive signal (spot #110 at amino acids 219–228) and two other positive signals (spot #68 at amino acids 135–144 and spot #144 at amino acids 287–296). No intense spots overlapped amino acid 358, which we spotted in both polymorphic forms and was included in numerous peptides. Results are from a 1-h exposure (similar results were obtained from an overnight exposure [not shown]).

David  Reich, et al. Am J Hum Genet. 2007 April;80(4):716-726.
3.
Figure  2. 

Figure 2. . From: Admixture Mapping of an Allele Affecting Interleukin 6 Soluble Receptor and Interleukin 6 Levels.

The 10%–30% of individuals with the highest IL-6 SR levels contributing most of the association. We rank-ordered 584 African Americans by their measured levels of IL-6 SR, from highest to lowest, not correcting for covariates. We ran ANCESTRYMAP, treating all samples as cases, and calculated the log factor of disease association for each sample under three models: (1) 2.5-fold increased risk for European ancestry associated with case status, the model that provided the strongest contribution to disease risk; (2) 1.5-fold increased risk for European ancestry; and (3) 1.25-fold increased risk for African ancestry. For model 1, the LOD score increased dramatically for the top 10% (peak LOD 6.57) of levels until the 30th percentile and then decreased, indicating that the signal was likely to be contributed only by the individuals with the highest 10%–30% of IL-6 SR levels.

David  Reich, et al. Am J Hum Genet. 2007 April;80(4):716-726.
4.
Figure  4. 

Figure 4. . From: Admixture Mapping of an Allele Affecting Interleukin 6 Soluble Receptor and Interleukin 6 Levels.

rs8192284 does not appear to affect levels of IL-6R protein on the cell surface. We measured expression of surface IL-6R protein on LCLs used in the HapMap Project and found no significant effect of the rs8192284 genotype. We plotted the distribution of IL-6R expression for unrelated European Americans from Utah (CEU), East Asians from Beijing (CHB) and Tokyo (JPT), and West Africans from Ibadan, Nigeria (YRI). The AA homozygotes are represented by red triangles, AC heterozygotes by green diamonds, and CC homozygotes by blue dots. The mean value of each genotype class is represented by a horizontal black line. P values for differences between each genotype class (t test) are reported. The low frequency of the C allele in the YRI samples (4%) limits the power of the analysis in this group (the frequencies are 35% in CEU and 43% in CHB and JPT).

David  Reich, et al. Am J Hum Genet. 2007 April;80(4):716-726.

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