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 Status: Updated 25 November 2011
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 rs3135388All2.27 (2.04-2.54)1.62E-481768 (A)n.a. (A) (A)A41.7
2 IL2RA rs2104286Caucasian0.82 (0.79-0.85)1.49E-2416087 (A)n.a. (A) (A)A21.5
3 IL7R rs6897932Caucasian0.84 (0.81-0.88)6.04E-2019322 (A)n.a. (A) (A)A17.0
4 TAGAP rs1738074All0.88 (0.86-0.91)1.78E-1531160 (A)n.a. (A) (A)A12.6
5 CLEC16A rs12708716All0.83 (0.79-0.87)2.00E-1513224 (A)n.a. (A) (A)A12.6
6 EVI5 rs11810217All1.15 (1.11-1.19)2.22E-1519829 (A)n.a. (A) (A)A12.5
7 GWA_16q24.1 rs17445836Caucasian0.83 (0.80-0.87)2.44E-159646 (A)n.a. (A) (A)A12.5
8 GWA_5p13.1 rs4613763All1.20 (1.14-1.25)9.44E-159813 (A)n.a. (A) (A)A11.9
9 TTC34 rs4648356All0.88 (0.85-0.91)1.53E-1423422 (A)n.a. (A) (A)A11.7
10 AHI1 rs11154801All1.13 (1.10-1.17)2.68E-1326365 (A)n.a. (A) (A)A10.5
11 GWA_3q24 rs669607All1.13 (1.09-1.17)2.61E-1234506 (A)n.a. (A) (A)A9.5
12 CD226 rs763361All1.13 (1.09-1.18)5.12E-1225992 (A)n.a. (A) (A)A9.2
13 CD5 rs650258All0.90 (0.87-0.92)6.15E-1227224 (A)n.a. (A) (A)A9.1
14 IL12B rs2546890All0.90 (0.87-0.93)1.37E-1134691 (A)n.a. (A) (A)A8.8
15 PLEK rs7595037All0.90 (0.87-0.93)2.62E-1132031 (A)n.a. (A) (A)A8.5
16 IL22RA2 rs17066096All1.13 (1.09-1.18)6.06E-1117910 (A)n.a. (A) (A)A8.2
17 NCOA5 rs2425752All1.11 (1.08-1.15)6.79E-1122524 (A)n.a. (A) (A)A8.1
18 STAT3 rs9891119All1.11 (1.08-1.14)1.02E-1027210 (A)n.a. (A) (A)A8.0
19 GWA_2p21 rs12466022All0.90 (0.87-0.93)1.48E-1021657 (A)n.a. (A) (A)A7.8
20 DKKL1 rs2303759All1.11 (1.08-1.15)1.85E-1021939 (A)n.a. (A) (A)A7.7
21 CYP24A1 rs2248359All0.90 (0.87-0.93)2.19E-1028392 (A)n.a. (A) (A)A7.7
22 TNFRSF1A rs1800693All1.11 (1.07-1.14)3.58E-1031650 (A)n.a. (A) (A)A7.4
23 TNFSF14 rs1077667All0.87 (0.83-0.91)6.57E-1015519 (A)n.a. (A) (A)A7.3
24 CD86 rs9282641All0.84 (0.79-0.89)9.73E-106814 (A)n.a. (A) (A)A7.1
25 CD58 rs12044852All0.72 (0.64-0.80)1.05E-092170 (A)n.a. (A) (A)A6.8
26 GWA_3q12.3 rs771767All1.11 (1.07-1.15)1.25E-0921947 (A)n.a. (A) (A)A6.9
27 SH2B3 rs3184504All1.13 (1.08-1.17)1.26E-0922559 (A)n.a. (A) (A)A7.0
28 SP140 rs10201872All1.14 (1.09-1.18)1.34E-0912328 (A)n.a. (A) (A)A6.9
29 GPR65 rs2119704All0.82 (0.77-0.88)1.54E-095395 (A)n.a. (A) (A)A6.9
30 CYP27B1 rs703842All0.85 (0.80-0.89)2.96E-099276 (A)n.a. (A) (A)A6.7
31 CD40 rs1569723All1.18 (1.12-1.25)3.06E-097252 (A)n.a. (A) (A)A6.6
32 MAPK1 rs2283792All0.91 (0.88-0.94)4.27E-0935611 (A)n.a. (A) (A)A6.4
33 ZFP36L1 rs4902647All0.91 (0.88-0.94)4.37E-0932662 (A)n.a. (A) (A)A6.4
34 AGAP2 rs12368653All1.11 (1.07-1.15)4.75E-0933404 (A)n.a. (A) (A)A6.4
35 RPS6KB1 rs180515All1.10 (1.06-1.13)1.08E-0826834 (A)n.a. (A) (A)A6.0
36 SOX8 rs2744148All1.12 (1.08-1.17)1.61E-0813392 (A)n.a. (A) (A)A5.9
37 MPV17L2 rs874628All0.9 (0.87-0.94)2.33E-0820284 (A)n.a. (A) (A)A5.7
38 PTPRK rs802734All0.91 (0.88-0.94)4.37E-0822252 (A)n.a. (A) (A)A5.4
39 ZMIZ1 rs1250550All1.1 (1.06-1.13)4.53E-0825562 (A)n.a. (A) (A)A5.4
40 PVR rs7255066All1.09 (1.06-1.13)7.94E-0821571 (A)n.a. (A) (A)A5.2
41 HHEX rs7923837All0.91 (0.88-0.95)1.24E-0727177 (A)0 (A)Low OR (C)C5.0
42 C1orf106 rs7522462All0.91 (0.87-0.94)1.43E-0719003 (A)0 (A)Low OR (C)C5.0
43 PKIA rs1520333All1.10 (1.06-1.14)1.57E-0719472 (A)0 (A)Low OR (C)C4.9
44 BACH2 rs12212193All1.09 (1.05-1.12)1.78E-0732715 (A)0 (A)Low OR (C)C4.8
45 MMEL1 rs3748816All0.84 (0.79-0.90)2.05E-076572 (A)0 (A) (A)A4.9
46 SLC30A7 rs11581062All1.11 (1.07-1.15)2.42E-0721176 (A)2 (A)Low OR (C)C4.8
47 BATF rs2300603All0.91 (0.88-0.94)2.73E-0718595 (A)0 (A)Low OR (C)C4.7
48 KIF21B rs12122721Caucasian0.85 (0.80-0.91)4.15E-076104 (A)0 (A) (A)A4.6
49 SAE1 rs307896All0.92 (0.89-0.95)4.17E-0722390 (A)0 (A)Low OR (C)C4.5
50 DLEU1 rs806321All0.92 (0.89-0.95)4.70E-0733939 (A)0 (A)Low OR (C)C4.4
51 MYC rs4410871All0.91 (0.88-0.94)5.16E-0719461 (A)0 (A)Low OR (C)C4.4
52 SYK rs290986All0.91 (0.87-0.94)6.47E-0714745 (A)0 (A)Low OR, Regr (C)C4.4
53 RGS14 rs4075958All1.09 (1.06-1.13)6.48E-0720301 (A)0 (A)Low OR, Regr (C)C4.3
54 DDAH1 rs233100All0.92 (0.89-0.95)7.13E-0731020 (A)0 (A)Low OR (C)C4.3
55 MERTK rs17174870All0.91 (0.88-0.94)8.39E-0717453 (A)0 (A)Low OR (C)C4.3
56 ZNF767 rs354033All0.91 (0.87-0.94)9.05E-0717923 (A)0 (A)Low OR (C)C4.2
57 CLECL1 rs10466829All0.92 (0.89-0.95)9.19E-0733686 (A)0 (A)Low OR (C)C4.2
58 MANBA rs228614All0.92 (0.89-0.95)9.73E-0733420 (A)0 (A)Low OR (C)C4.1
59 TYK2 rs34536443All0.72 (0.64-0.83)1.19E-061773 (A)37 (B) (A)B4.0
60 ZBTB46 rs6062314All0.86 (0.81-0.92)1.26E-065789 (A)0 (A) (A)A4.2
61 CDC37 rs8112449All0.92 (0.89-0.95)1.68E-0624428 (A)0 (A)Low OR (C)C3.9
62 NDFIP1 rs1062158All0.93 (0.9-0.96)2.10E-0626977 (A)0 (A)Low OR (C)C3.8
63 MAP3K14 rs4792814All0.93 (0.9-0.96)2.21E-0628834 (A)0 (A)Low OR (C)C3.8
64 RGS1 rs2760524All0.87 (0.82-0.92)2.98E-065101 (A)0 (A) (A)A3.8
65 TMEM39A rs1132200All0.85 (0.79-0.91)4.30E-064519 (A)9 (A) (A)A3.7
66 MALT1 rs7238078All0.91 (0.87-0.95)5.97E-0616103 (A)0 (A)Low OR (C)C3.5
67 CARD11 rs1843938All1.08 (1.04-1.11)6.02E-0630758 (A)0 (A)Low OR (C)C3.4
68 MAF rs386965All1.09 (1.05-1.13)7.47E-0617169 (A)0 (A)Low OR (C)C3.3
69 IRF5 rs4728142All1.15 (1.08-1.22)9.51E-067905 (A)0 (A)Low OR (C)C3.4

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 2550%, 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.
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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Top Results Details
2. IL2RA
3. IL7R
5. CLEC16A
6. EVI5
7. GWA_16q24.1
8. GWA_5p13.1
9. TTC34
10. AHI1   
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Genes: 809
Polymorphisms: 2907
Meta-analyses: 324
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