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| Status: |
Updated 25 November 2011 |
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| Ranking based on HuGENet interim guidelines for the assessment of genetic association studies |
| # |
Gene |
Polymorphism |
Ethnicity |
OR (95% CI) |
P-value |
N minor (Grade) |
I2 (Grade) |
Bias Reason (Grade) |
Overall Grade |
Bayes Factor (log10) |
| 1 |
HLA-DRB1 |
rs3135388 | All | 2.27 (2.04-2.54) | 1.62E-48 | 1768 (A) | n.a. (A) | (A) | A | 41.7 |
| 2 |
IL2RA |
rs2104286 | Caucasian | 0.82 (0.79-0.85) | 1.49E-24 | 16087 (A) | n.a. (A) | (A) | A | 21.5 |
| 3 |
IL7R |
rs6897932 | Caucasian | 0.84 (0.81-0.88) | 6.04E-20 | 19322 (A) | n.a. (A) | (A) | A | 17.0 |
| 4 |
TAGAP |
rs1738074 | All | 0.88 (0.86-0.91) | 1.78E-15 | 31160 (A) | n.a. (A) | (A) | A | 12.6 |
| 5 |
CLEC16A |
rs12708716 | All | 0.83 (0.79-0.87) | 2.00E-15 | 13224 (A) | n.a. (A) | (A) | A | 12.6 |
| 6 |
EVI5 |
rs11810217 | All | 1.15 (1.11-1.19) | 2.22E-15 | 19829 (A) | n.a. (A) | (A) | A | 12.5 |
| 7 |
GWA_16q24.1 |
rs17445836 | Caucasian | 0.83 (0.80-0.87) | 2.44E-15 | 9646 (A) | n.a. (A) | (A) | A | 12.5 |
| 8 |
GWA_5p13.1 |
rs4613763 | All | 1.20 (1.14-1.25) | 9.44E-15 | 9813 (A) | n.a. (A) | (A) | A | 11.9 |
| 9 |
TTC34 |
rs4648356 | All | 0.88 (0.85-0.91) | 1.53E-14 | 23422 (A) | n.a. (A) | (A) | A | 11.7 |
| 10 |
AHI1 |
rs11154801 | All | 1.13 (1.10-1.17) | 2.68E-13 | 26365 (A) | n.a. (A) | (A) | A | 10.5 |
| 11 |
GWA_3q24 |
rs669607 | All | 1.13 (1.09-1.17) | 2.61E-12 | 34506 (A) | n.a. (A) | (A) | A | 9.5 |
| 12 |
CD226 |
rs763361 | All | 1.13 (1.09-1.18) | 5.12E-12 | 25992 (A) | n.a. (A) | (A) | A | 9.2 |
| 13 |
CD5 |
rs650258 | All | 0.90 (0.87-0.92) | 6.15E-12 | 27224 (A) | n.a. (A) | (A) | A | 9.1 |
| 14 |
IL12B |
rs2546890 | All | 0.90 (0.87-0.93) | 1.37E-11 | 34691 (A) | n.a. (A) | (A) | A | 8.8 |
| 15 |
PLEK |
rs7595037 | All | 0.90 (0.87-0.93) | 2.62E-11 | 32031 (A) | n.a. (A) | (A) | A | 8.5 |
| 16 |
IL22RA2 |
rs17066096 | All | 1.13 (1.09-1.18) | 6.06E-11 | 17910 (A) | n.a. (A) | (A) | A | 8.2 |
| 17 |
NCOA5 |
rs2425752 | All | 1.11 (1.08-1.15) | 6.79E-11 | 22524 (A) | n.a. (A) | (A) | A | 8.1 |
| 18 |
STAT3 |
rs9891119 | All | 1.11 (1.08-1.14) | 1.02E-10 | 27210 (A) | n.a. (A) | (A) | A | 8.0 |
| 19 |
GWA_2p21 |
rs12466022 | All | 0.90 (0.87-0.93) | 1.48E-10 | 21657 (A) | n.a. (A) | (A) | A | 7.8 |
| 20 |
DKKL1 |
rs2303759 | All | 1.11 (1.08-1.15) | 1.85E-10 | 21939 (A) | n.a. (A) | (A) | A | 7.7 |
| 21 |
CYP24A1 |
rs2248359 | All | 0.90 (0.87-0.93) | 2.19E-10 | 28392 (A) | n.a. (A) | (A) | A | 7.7 |
| 22 |
TNFRSF1A |
rs1800693 | All | 1.11 (1.07-1.14) | 3.58E-10 | 31650 (A) | n.a. (A) | (A) | A | 7.4 |
| 23 |
TNFSF14 |
rs1077667 | All | 0.87 (0.83-0.91) | 6.57E-10 | 15519 (A) | n.a. (A) | (A) | A | 7.3 |
| 24 |
CD86 |
rs9282641 | All | 0.84 (0.79-0.89) | 9.73E-10 | 6814 (A) | n.a. (A) | (A) | A | 7.1 |
| 25 |
CD58 |
rs12044852 | All | 0.72 (0.64-0.80) | 1.05E-09 | 2170 (A) | n.a. (A) | (A) | A | 6.8 |
| 26 |
GWA_3q12.3 |
rs771767 | All | 1.11 (1.07-1.15) | 1.25E-09 | 21947 (A) | n.a. (A) | (A) | A | 6.9 |
| 27 |
SH2B3 |
rs3184504 | All | 1.13 (1.08-1.17) | 1.26E-09 | 22559 (A) | n.a. (A) | (A) | A | 7.0 |
| 28 |
SP140 |
rs10201872 | All | 1.14 (1.09-1.18) | 1.34E-09 | 12328 (A) | n.a. (A) | (A) | A | 6.9 |
| 29 |
GPR65 |
rs2119704 | All | 0.82 (0.77-0.88) | 1.54E-09 | 5395 (A) | n.a. (A) | (A) | A | 6.9 |
| 30 |
CYP27B1 |
rs703842 | All | 0.85 (0.80-0.89) | 2.96E-09 | 9276 (A) | n.a. (A) | (A) | A | 6.7 |
| 31 |
CD40 |
rs1569723 | All | 1.18 (1.12-1.25) | 3.06E-09 | 7252 (A) | n.a. (A) | (A) | A | 6.6 |
| 32 |
MAPK1 |
rs2283792 | All | 0.91 (0.88-0.94) | 4.27E-09 | 35611 (A) | n.a. (A) | (A) | A | 6.4 |
| 33 |
ZFP36L1 |
rs4902647 | All | 0.91 (0.88-0.94) | 4.37E-09 | 32662 (A) | n.a. (A) | (A) | A | 6.4 |
| 34 |
AGAP2 |
rs12368653 | All | 1.11 (1.07-1.15) | 4.75E-09 | 33404 (A) | n.a. (A) | (A) | A | 6.4 |
| 35 |
RPS6KB1 |
rs180515 | All | 1.10 (1.06-1.13) | 1.08E-08 | 26834 (A) | n.a. (A) | (A) | A | 6.0 |
| 36 |
SOX8 |
rs2744148 | All | 1.12 (1.08-1.17) | 1.61E-08 | 13392 (A) | n.a. (A) | (A) | A | 5.9 |
| 37 |
MPV17L2 |
rs874628 | All | 0.9 (0.87-0.94) | 2.33E-08 | 20284 (A) | n.a. (A) | (A) | A | 5.7 |
| 38 |
PTPRK |
rs802734 | All | 0.91 (0.88-0.94) | 4.37E-08 | 22252 (A) | n.a. (A) | (A) | A | 5.4 |
| 39 |
ZMIZ1 |
rs1250550 | All | 1.1 (1.06-1.13) | 4.53E-08 | 25562 (A) | n.a. (A) | (A) | A | 5.4 |
| 40 |
PVR |
rs7255066 | All | 1.09 (1.06-1.13) | 7.94E-08 | 21571 (A) | n.a. (A) | (A) | A | 5.2 |
| 41 |
HHEX |
rs7923837 | All | 0.91 (0.88-0.95) | 1.24E-07 | 27177 (A) | 0 (A) | Low OR (C) | C | 5.0 |
| 42 |
C1orf106 |
rs7522462 | All | 0.91 (0.87-0.94) | 1.43E-07 | 19003 (A) | 0 (A) | Low OR (C) | C | 5.0 |
| 43 |
PKIA |
rs1520333 | All | 1.10 (1.06-1.14) | 1.57E-07 | 19472 (A) | 0 (A) | Low OR (C) | C | 4.9 |
| 44 |
BACH2 |
rs12212193 | All | 1.09 (1.05-1.12) | 1.78E-07 | 32715 (A) | 0 (A) | Low OR (C) | C | 4.8 |
| 45 |
MMEL1 |
rs3748816 | All | 0.84 (0.79-0.90) | 2.05E-07 | 6572 (A) | 0 (A) | (A) | A | 4.9 |
| 46 |
SLC30A7 |
rs11581062 | All | 1.11 (1.07-1.15) | 2.42E-07 | 21176 (A) | 2 (A) | Low OR (C) | C | 4.8 |
| 47 |
BATF |
rs2300603 | All | 0.91 (0.88-0.94) | 2.73E-07 | 18595 (A) | 0 (A) | Low OR (C) | C | 4.7 |
| 48 |
KIF21B |
rs12122721 | Caucasian | 0.85 (0.80-0.91) | 4.15E-07 | 6104 (A) | 0 (A) | (A) | A | 4.6 |
| 49 |
SAE1 |
rs307896 | All | 0.92 (0.89-0.95) | 4.17E-07 | 22390 (A) | 0 (A) | Low OR (C) | C | 4.5 |
| 50 |
DLEU1 |
rs806321 | All | 0.92 (0.89-0.95) | 4.70E-07 | 33939 (A) | 0 (A) | Low OR (C) | C | 4.4 |
| 51 |
MYC |
rs4410871 | All | 0.91 (0.88-0.94) | 5.16E-07 | 19461 (A) | 0 (A) | Low OR (C) | C | 4.4 |
| 52 |
SYK |
rs290986 | All | 0.91 (0.87-0.94) | 6.47E-07 | 14745 (A) | 0 (A) | Low OR, Regr (C) | C | 4.4 |
| 53 |
RGS14 |
rs4075958 | All | 1.09 (1.06-1.13) | 6.48E-07 | 20301 (A) | 0 (A) | Low OR, Regr (C) | C | 4.3 |
| 54 |
DDAH1 |
rs233100 | All | 0.92 (0.89-0.95) | 7.13E-07 | 31020 (A) | 0 (A) | Low OR (C) | C | 4.3 |
| 55 |
MERTK |
rs17174870 | All | 0.91 (0.88-0.94) | 8.39E-07 | 17453 (A) | 0 (A) | Low OR (C) | C | 4.3 |
| 56 |
ZNF767 |
rs354033 | All | 0.91 (0.87-0.94) | 9.05E-07 | 17923 (A) | 0 (A) | Low OR (C) | C | 4.2 |
| 57 |
CLECL1 |
rs10466829 | All | 0.92 (0.89-0.95) | 9.19E-07 | 33686 (A) | 0 (A) | Low OR (C) | C | 4.2 |
| 58 |
MANBA |
rs228614 | All | 0.92 (0.89-0.95) | 9.73E-07 | 33420 (A) | 0 (A) | Low OR (C) | C | 4.1 |
| 59 |
TYK2 |
rs34536443 | All | 0.72 (0.64-0.83) | 1.19E-06 | 1773 (A) | 37 (B) | (A) | B | 4.0 |
| 60 |
ZBTB46 |
rs6062314 | All | 0.86 (0.81-0.92) | 1.26E-06 | 5789 (A) | 0 (A) | (A) | A | 4.2 |
| 61 |
CDC37 |
rs8112449 | All | 0.92 (0.89-0.95) | 1.68E-06 | 24428 (A) | 0 (A) | Low OR (C) | C | 3.9 |
| 62 |
NDFIP1 |
rs1062158 | All | 0.93 (0.9-0.96) | 2.10E-06 | 26977 (A) | 0 (A) | Low OR (C) | C | 3.8 |
| 63 |
MAP3K14 |
rs4792814 | All | 0.93 (0.9-0.96) | 2.21E-06 | 28834 (A) | 0 (A) | Low OR (C) | C | 3.8 |
| 64 |
RGS1 |
rs2760524 | All | 0.87 (0.82-0.92) | 2.98E-06 | 5101 (A) | 0 (A) | (A) | A | 3.8 |
| 65 |
TMEM39A |
rs1132200 | All | 0.85 (0.79-0.91) | 4.30E-06 | 4519 (A) | 9 (A) | (A) | A | 3.7 |
| 66 |
MALT1 |
rs7238078 | All | 0.91 (0.87-0.95) | 5.97E-06 | 16103 (A) | 0 (A) | Low OR (C) | C | 3.5 |
| 67 |
CARD11 |
rs1843938 | All | 1.08 (1.04-1.11) | 6.02E-06 | 30758 (A) | 0 (A) | Low OR (C) | C | 3.4 |
| 68 |
MAF |
rs386965 | All | 1.09 (1.05-1.13) | 7.47E-06 | 17169 (A) | 0 (A) | Low OR (C) | C | 3.3 |
| 69 |
IRF5 |
rs4728142 | All | 1.15 (1.08-1.22) | 9.51E-06 | 7905 (A) | 0 (A) | Low OR (C) | C | 3.4 |
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Only meta-analysis results with P-values <1.00E-05 are displayed in this table. Loci are ranked by statistical significance (P-value). For loci containing more than one polymorphism showing significant association after Bonferroni correction, only the polymorphism with the smallest P-value is displayed.
Furthermore, each nominally significant meta-analysis in MSGene is graded based on HuGENet (Human Genome Epidemiology Network) interim criteria for the assessment of cumulative evidence of genetic associations (Ioannidis et al, 2008; Khoury et al, 2009). These criteria take into account amount of evidence (i.e. sample size, measured as "N minor"), consistency of replication (i.e. heterogeneity across studies, measured as "I2"), and protection from bias ("Bias reason").
1. Amount of evidence: grade "A" is assigned when the total number of minor alleles of cases and controls combined in the meta-analyses exceeds 1,000, "B" when it is between 100 and 1,000, and "C" when it is less than 100.
2. Consistency of replication: grade "A" is assigned for I2 point estimates <25%, "B" for I2 values of 25–50%, and "C" for I2 values >50%. This criterion does not apply to meta-analyses with a P-value <1x10-7 after exclusion of the initial studie(s), as described in Khoury et al, 2009.
3. Protection from bias: the following potential reasons for bias in the meta-analysis results are systematically assessed: summary OR <1.15 ("Low OR"), loss of significance after exclusion of first study ("F"), loss of significance after exclusion of studies with deviations from Hardy-Weinberg equilibrium in control populations ("HWE"), or evidence for positive publication bias using a modified regression test ("Regr"). If none of the latter conditions are met grade "A" is assigned, otherwise grade "C".
Overall epidemiological credibility is graded as "A" (=strong) if associations received three A grades, "B" (=moderate) if they received at least one B grade but no C grades, and "C" (=weak) if they received a C grade in any of the three assessment criteria.
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Reference
Ioannidis JP, Boffetta P, Little J, O'Brien TR, Uitterlinden AG, Vineis P, Balding DJ, Chokkalingam A, Dolan SM, Flanders WD, Higgins JP, McCarthy MI, McDermott DH, Page GP, Rebbeck TR, Seminara D, Khoury MJ (2008) "Assessment of cumulative evidence on genetic associations: interim guidelines." Int J Epidemiol 37(1):120-32. Abstract
Khoury MJ, Bertram L, Boffetta P, Butterworth AS, Chanock SJ, Dolan SM, Fortier I, Garcia-Closas M, Gwinn M, Higgins JP, Janssens AC, Ostell J, Owen RP, Pagon RA, Rebbeck TR, Rothman N, Bernstein JL, Burton PR, Campbell H, Chockalingam A, Furberg H, Little J, O'Brien TR, Seminara D, Vineis P, Winn DM, Yu W, Ioannidis JP (2009) "Genome-wide association studies, field synopses, and the development of the knowledge base on genetic variation and human diseases." Am J Epidemiol 170(3):269-79. Abstract
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