Table 1.
Genome-wide Significant Loci with Additional Modifier Haplotypes Identified by Conditional Analysis
| Chr | Modifiera | Top SNP | BP (hg19) | Minor Allele | MAF (%) | Continuous Analysis |
Dichotomous Analysis |
Candidate Modifier Genes |
|||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall |
p Value | Males |
p Value | Females |
p Value | Overall |
|||||||
| Effect Size (years) | Effect Size (years) | Effect Size (years) | p Value | ||||||||||
| 1 | 1AM1b | rs567500111 | 164283625 | A | 0.3 | −4.4 | 6.9E-06 | −8.0 | 2.0E-08 | −1.3 | 3.5E-01 | 6.5E-02 | |
| 2 | 2AM1 | rs3791767 | 190639915 | C | 20.7 | −0.8 | 6.3E-08 | −0.9 | 6.3E-06 | −0.7 | 9.5E-04 | 4.9E-11 | PMS1 |
| 3 | 3AM1 | rs1799977 | 37053568 | G | 31.0 | 0.8 | 5.1E-10 | 0.6 | 1.3E-03 | 0.9 | 3.3E-08 | 7.3E-10 | MLH1 |
| 5AM1 | rs701383 | 79913275 | A | 25.7 | −0.8 | 5.5E-10 | −0.4 | 2.1E-02 | −1.2 | 4.6E-11 | 1.0E-10 | ||
| 5 | 5AM2 | rs113361582 | 80086504 | G | 0.3 | 6.1 | 1.3E-09 | 6.1 | 3.4E-05 | 6.4 | 3.1E-06 | 6.6E-05 | MSH3, DHFR |
| 5AM3 | rs1650742 | 79990883 | G | 33.1 | 0.6 | 1.6E-06 | 0.3 | 7.3E-02 | 0.9 | 2.2E-07 | 1.0E-06 | ||
| 5 | 5BM1 | rs79727797 | 145886836 | A | 2.4 | 2.3 | 3.8E-10 | 2.7 | 2.5E-07 | 2.0 | 1.1E-04 | 5.8E-09 | TCERG1 |
| 7 | 7AM1 | rs74302792 | 6079993 | A | 15.9 | 0.8 | 7.4E-08 | 0.9 | 4.1E-05 | 0.8 | 2.8E-04 | 1.3E-08 | PMS2 |
| 8 | 8AM1 | rs79136984 | 103213640 | T | 8.2 | −1.2 | 3.6E-09 | −1.4 | 1.9E-06 | −1.0 | 2.3E-04 | 4.7E-09 | RRM2B, UBR5 |
| 11 | 11AM1 | rs7936234 | 96106737 | A | 19.6 | 0.6 | 1.7E-05 | 0.7 | 5.5E-04 | 0.6 | 5.5E-03 | 1.3E-08 | CCDC82 |
| 11 | 11BM1b | rs79714630 | 7303052 | G | 0.1 | −9.6 | 1.1E-08 | −10.6 | 7.0E-06 | −8.6 | 3.1E-04 | 3.8E-02 | SYT9 |
| 12 | 12AM1b | rs140253376 | 108992727 | A | 0.2 | −6.1 | 8.3E-06 | −10.1 | 3.0E-08 | −1.2 | 5.8E-01 | 6.9E-03 | |
| 15AM1 | rs150393409 | 31202961 | A | 1.4 | −5.2 | 1.8E-28 | −5.1 | 6.3E-14 | −5.4 | 2.1E-16 | 1.6E-17 | ||
| 15 | 15AM2 | rs35811129 | 31241346 | A | 27.5 | 1.3 | 9.4E-26 | 1.1 | 1.3E-09 | 1.6 | 1.8E-19 | 8.2E-25 | FAN1 |
| 15AM3 | rs151322829 | 31197995 | T | 0.7 | −3.8 | 1.4E-08 | −4.1 | 1.0E-05 | −3.5 | 2.3E-04 | 4.3E-07 | ||
| 15AM4 | rs34017474 | 31230611 | C | 38.2 | 0.8 | 8.5E-11 | 0.5 | 3.0E-03 | 1.0 | 1.1E-10 | 2.6E-11 | ||
| 16 | 16AM1b | rs187055476 | 27873637 | G | 0.3 | −6.1 | 5.5E-09 | −7.2 | 7.1E-07 | −5.1 | 8.1E-04 | 2.2E-04 | GSG1L |
| 18 | 18AM1b | rs530017366 | 56126806 | T | 0.2 | −5.1 | 1.2E-04 | −12.0 | 8.2E-09 | −0.1 | 9.5E-01 | 4.3E-01 | |
| 19AM1 | rs274883 | 48622545 | G | 16.7 | 0.9 | 5.3E-09 | 0.8 | 7.3E-05 | 0.9 | 1.8E-05 | 1.1E-07 | ||
| 19 | 19AM2 | rs3730945 | 48645976 | G | 37.1 | −0.6 | 5.8E-07 | −0.5 | 6.8E-03 | −0.7 | 1.2E-05 | 2.4E-06 | LIG1 |
| 19AM3 | rs145821638 | 48620943 | A | 0.1 | 7.7 | 1.5E-06 | 3.8 | 1.3E-01 | 10.2 | 1.1E-06 | 7.5E-03 | ||
Ref, reference; Alt, Alternate, MAF, minor allele frequency. See also Figure S3 and Tables S2 and S3–S5.
a
For clarity of presentation, to avoid confusion with haplotypes defined by different means, and in anticipation of discovering additional modifier loci on some of these chrs, we have adopted a naming system for the haplotypes marking the modifier effects that indicates the chr number, the order of discovery of the locus on that chr (i.e., A, B, etc.) and a sequential number for each modifier at that locus (i.e., M1, M2, M3, etc.).
b
Locus supported by a single rare SNP allele in continuous analysis.