Table 3.
Literature-reported candidate genes for peripheral artery disease (PAD) and coronary artery disease (CAD) and their association with ankle-brachial index (ABI) in the CHARGE GWAS discovery sample (population isolates excluded) with FDR <0.10†.
| SNP | Chr | Physical Position | Closest Gene | Risk/Non-risk Allele | Risk Allele frequency | N | Beta | SE | P value* | # of effective loci ‡ | P value corrected‡ | False discovery rate‡ |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PAD genes |
|
|||||||||||
| rs10757269 | 9 | 22,062,264 | CDKN2B | G/A | 0.51 | 35036 | −0.006 | 0.001 | 2.50E-08 | 69 | 1.70E-06 | 9.32E-05
|
| rs3794624 | 16 | 87,244,575 | CYBA | G/A | 0.34 | 31035 | −0.005 | 0.001 | 6.30E-05 | 58 | 3.60E-03 | 0.0665
|
| rs13290547 | 9 | 123,527,316 | DAB2IP | T/C | 0.06 | 32135 | −0.009 | 0.002 | 3.60E-05 | 97 | 3.50E-03 | 0.0665
|
| CAD genes |
|
|||||||||||
| rs4977574 | 9 | 22,088,574 | CDKN2B | G/A | 0.49 | 35411 | −0.0047 | 0.001 | 2.33E-06 | - | - | 6.52E-05
|
| rs1122608 | 19 | 11,024,601 | LDLR | G/T | 0.74 | 35384 | −0.0035 | 0.001 | 2.56E-03 | - | - | 0.036 |
P value from Discovery GWAS of ABI
Candidate genes for PAD were selected for testing with ABI if an association study with at least 100 cases and 100 controls was available in the literature independent of whether the study was positive or negative. Genes for CAD were only considered for testing with ABI if they were identified by recent GWAS to be genome-wide significantly associated with CAD. The table shows only the genes which showed an experiment-wise significant association with ABI after correction for multiple testing. The entire list of genes can be seen in Supplementary tables 10 and 11 for PAD and CAD genes, respectively.
Due to the high correlation of imputed genotype scores, the effective number of loci was calculated for each PAD gene region (31) using the genotype scores from the KORA F4 Study. Bonferroni correction of p-values was then applied in each region using this number. Furthermore, the corrected P value thresholds of significance for 28 CAD loci (tested in Suppl Table 11, α=0.05/28, 1.85 x 10−3) and 55 PAD loci (tested in Suppl Table 10, α=0.05/effective number of loci) were calculated. We also calculated a false discovery rate (FDR) using the corrected p-values accounting for the number of gene regions examined. An FDR <0.10 defined evidence of a significant association.