Table 2.
Gene (locus) | SNP (maj/min allelea) | Location (putative miRs) b | OR (95% CI) reported by Liang et al (Ref. 3) | MAF c | Pooled OR (95% CI), adjusted for study d | P | Pooled OR (95% CI), adjusted for study and ancestry e | P |
---|---|---|---|---|---|---|---|---|
miRNA processing | ||||||||
DDX20 (1p21,1-p13.2) | rs197414 (C/A) f | Missense | 0.69 (0.48–0.99) | 0.13 | 1.02 (0.92,1.12) | 0.70 | 1.04 (0.94,1.15) | 0.49 |
DROSHA (5p13.3) | rs9292427 (C/T)g | Intron | 0.71 (0.51–0.99) | 0.46 | 1.01 (0.95,1.08) | 0.72 | 1.01 (0.94,1.08) | 0.79 |
GEMIN4 (17p13) | rs2740349 (A/C) h | exon 1, ns | 0.70 (0.51–0.96) | 0.18 | 0.99 (0.92,1.09) | 0.97 | 1.02 (0.93,1.11) | 0.71 |
rs2740351 (T/C) i | flanks 5′UTR | 0.71 (0.57–0.87) | 0.45 | 0.98 (0.91,1.04) | 0.46 | 1.00 (0.94,1.07) | 0.98 | |
rs7813 (T/G) i | exon 1, ns | 0.71 (0.57–0.88) | 0.46 | 0.97 (0.91,1.04) | 0.38 | 1.00 (0.93,1.07) | 0.91 | |
XPO5 (6p21.1) | rs2257082 (C/A) | exon 1, ss | 0.73 (0.54–0.99) | 0.27 | 0.99 (0.92,1.07) | 0.87 | 1.00 (0.93,1.08) | 0.95 |
miRNA binding sites | ||||||||
CAV1 (7q31.1) | rs9920 (G/A) | 3′UTR (miR 630) | 1.50 (1.04–2.17) | 0.10 | 1.13 (1.10,1.26) | 0.03 | 1.06 (0.95,1.19) | 0.29 |
COL18A1 (21q22.3) | rs7499 (G/A) | 3′UTR (miR-594) | 1.47 (1.07–2.02) | 0.42 c | 0.98 (0.92,1.05) | 0.57 | 0.98 (0.92,1.05) | 0.50 |
E2F2 (1p36) | rs2075993 (A/C) j | 3′UTR (miR-663,486-3p) | 1.24 (1.00–1.54) | 0.48 | 1.01 (0.95,1.08) | 0.67 | 1.01 (0.94,1.08) | 0.87 |
ILIR1 (2q12) | rs3917328 (C/T) | 3′UTR (miR-335, 31) | 1.65 (1.03–2.64) | 0.05 c | 1.06 (0.91,1.23) | 0.49 | 1.00 (0.86,1.17) | 0.99 |
KRAS (12p12.1) | rs13096 (A/G) k | 3′UTR (miR-1244) | 1.26 (1.01–1.57) | 0.45 | 1.00 (0.94,1.07) | 0.94 | 0.99 (0.93,1.06) | 0.85 |
UGT2A3 (4q13.2) | rs17147016 (T/A) h | 3′UTR (miR-224, 1279) | 1.47 (1.08–2.01) | 0.19 c | 1.02 (0.93,1.11) | 0.70 | 1.01 (0.93,1.10) | 0.88 |
Abbreviations: US-CAN=United States-Canada; UK=United Kingdom; POL=Poland; maj=major; min=minor; miR=miRNA; UTR= untranslated region; ns=non- synonymous SNP; ss=synonymous SNP; OR (CI) =odds ratio (confidence interval); MAF=minor allele frequency among all controls; all P-values are two-sided.
The major allele represents the most frequently-occurring allele and serves as the reference allele during modeling.
SNP location derived from Illumina annotation files, HapMap2 data (http://hapmap.ncbi.nlm.nih.gov/), and dbSNP (http://www.ncbi.nlm.nih.gov/projects/SNP/). SNPinfo http://snpinfo.niehs.nih.gov/ and the PolymiRTS database (http://compbio.uthsc.edu/miRSNP) were used to predict miRNAs whose binding activity may be altered due to the SNP location.
Genotype data was imputed for all participants using MACH version 1.0.16 using phased data from HapMap release 22 (genome build 36) derived from individuals with European ancestry (CEU).
Pooled OR and 95% CI estimated using a log-additive model adjusted for study (US-CAN, UK, POL)
Pooled OR and 95% CI estimated using a log-additive model adjusted for study and the first two principal components representing European ancestry
DDX20 rs19714 is in linkage disequilibrium (LD) (r2 =0.90) with rs197383 identified by Liang et al.
DROSHA rs9292427 is in LD (r2 =0.98) with rs4867329 identified by Liang et al.
SNP deviates from Hardy Weinberg Equilibrium among all controls with PHWE values of 0.020 for rs607613, 0.040 for rs615435, 0.013 for rs2740349, 0.004 for rs3732133, and 0.034 for rs17147016, respectively.
GEMIN4 SNP pair in LD (r2 =1)
E2F2 SNP pair in LD (r2 =0.97)
KRAS rs13096 is in LD (r2 =1) with rs10771184 identified by Liang et al.