Table 2. AAMD-associated sequence variants (P≤0.005)* resident in genes of the STKE JNK MAPK pathway.
SNP Feature | OR (95%CI) | ||||||
Symbol | SNP Ref. | Alleles | Cohort 1 | Cohort 2 | Cohort 3 | ORmeta | P meta |
GAB1 | rs3805236 | T|C | 0.68(0.53,0.87) | 0.68(0.46,1.00) | 0.94(0.66,1.32) | 0.74 | 1.01×10−3 |
MAP3K4 | rs1488 | G|A | 1.48(1.16,1.90) | 1.58(1.07,2.36) | 1.04(0.72,1.49) | 1.37 | 6.47×10−4 |
rs3798917 | G|T | 1.45(1.10,1.90) | 1.29(0.84,1.98) | 1.44(0.97,2.12) | 1.41 | 6.87×10−4 | |
MAP3K5 | rs1011969 | A|C | 1.30(1.00,1.70) | 1.01(0.65,1.57) | 1.97(1.31,2.94) | 1.37 | 2.15×10−3 |
rs9402839 | A|G | 0.72(0.54,0.95) | 0.72(0.46,1.14) | 0.78(0.51,1.22) | 0.73 | 4.29×10−3 | |
MAP3K9 | rs10483834 | G|A | 0.80(0.63,1.03) | 0.69(0.47,1.03) | 0.69(0.48,0.99) | 0.75 | 1.90×10−3 |
JNK3A1 | rs9307016 | C|T | 0.76(0.59,0.99) | 0.72(0.47,1.09) | 0.69(0.46,1.03) | 0.74 | 2.02×10−3 |
rs7440491 | C|A | 0.77(0.60,0.98) | 0.84(0.57,1,25) | 0.71(0.49,1.04) | 0.77 | 4.81×10−3 | |
rs1469869 | T|C | 1.29(0.99,1.62) | 1.46(0.96,2.20) | 1.35(0.91,1.99) | 1.34 | 3.02×10−3 | |
NR2C2 | rs1344825 | C|T | 0.84(0.66,1.06) | 0.54(0.35,0.83) | 0.74(0.52,1.09) | 0.75 | 2.05×10−3 |
Note: Odds ratios (ORs) and 95% confidence intervals (95% CIs) were computed, respectively, in Cohort 1/2/3 with age-, sex-, and smoking-adjusted logistic regression models comparing 675/227/275 people with advanced AMD (AAMD) to 512/198/314 of their AMD-free peers, aged >65 years at the time of genotyping. Participants from Cohort 1 were examined at the University of Michigan Ann Arbor. Those in Cohort 2 were examined at the University of Pennsylvania in Philadelphia. Those in Cohort 3 were examined at the Mayo Clinic in Rochester, Minnesota. Alleles are listed as minor|major.
Only SNPs significant at P≤0.002 were considered as AAMD-related in the pathway analysis. In most cases dominant models of inheritance (grouping minor allele homozygotes with heterozygotes) yielded strongest relationships – ORs reported here are from analyses using this model, with the exception of that for NR2C2 (here the additive model was used). Table S3 contains allelic frequencies of variants in this table.