Protective chromosome 1q32 haplotypes mitigate risk for age-related macular degeneration associated with the CFH-CFHR5 and ARMS2/HTRA1 loci

Table 3 Haplotype analysis of the CFH-CFHR5 extended region in the combined Utah/Iowa cohort using all common credible sets of variants independently associated with AMD (IAMDGC Locus 1.1, 1.2, 1.5 and 1.6) and comparison with the IAMDGC cohort (17,832 controls, 16,144 cases). Frequencies among Caucasians from the 1000 Genomes Project phase 3 (EUR), denoted 1000 G, are also provided

The labelling and numbering of haplotypes follows that of the haplotype analysis of the IAMDGC cohort [41]. For consistency with this analysis, the rare variant rs35292876 (IAMDGC Locus # 1.7 with minor allele T, MAF_controls = 0.005; MAF_cases = 0.014; OR 2.99 [1.73; 5.17], p = 8.8e−5 in our cohort and MAF_controls = 0.009; MAF_cases: 0.021; OR 2.42, p = 8.2e−37 in the IAMDGC study) was also included. The rs35292876 minor allele exists exclusively on a low-frequency haplotype containing a C (risk) allele at rs1061170. While this variant may modulate risk, its frequency and effect size are therefore accounted for by haplotypes with a C allele at rs1061170. Haplotypes in the IAMDGC cohort used rs570618 in place of rs1061170 (r² = 0.9914, Dʹ = 1.0), rs10922109 in place of rs14100996 (r² = 0.9919, Dʹ = 0.9959) and rs6677604 in place of rs12144939
⁽¹⁾Rare (frequency of 0.5%) among Utah residents in the USA (CEU) of the 1000 Genomes Project phase 3. ⁽²⁾Frequencies among cases and controls were too small to generate odds ratios *Based on the \({\mathrm{\rm X}}^{2}\)-square test with one degree of freedom. **Bonferroni correction for multiple testing of 9 haplotypes = 0.0056 (0.05/9)

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