Statistics

1 . Different types of Research

CGAa	GWAb	CGLAc	Total
640	25	21	686

^aCGA : candidate gene association studies

^bGWA : genome-wide association studies

^cCGLA : candidate gene linkage analysis studies

2 . The statistical information of polymorphisms

SNPa	HLA alleleb	minisatellitec or microsatellited	others
2933	175	72	55

^aSNP : Single nucleotide polymorphism

^bHLA : human leukocyte antigen

^cminisatellite : variable number of tandem repeats

^dmicrosatellite : short tandem repeat,STR,SSR

3 . Hotspots for rheumatoid arthritis

Fig.1. Distribution of rheumatoid arthritis (RA) related polymorphisms , genes and references on chromosomes in RADB. 1-22 represents 22 pairs of autosomes, ‘X’ represents X chromosome. The Y-axis indicates number of polymorphisms , genes or references.

   We can clearly see that polymorphisms mainly distribute on chromosome 6, chromosome 1, chromosome 2 , chromosome 9 and chromosome 16 . The distribution of genes is similar to the distribution of polymorphisms. There are more genes on chromosome 1 , chromosome 2 and chromosome 6 than others.

Table 1. The statistical information of top 50 cytoband locations in RADB (sorted by number of references)

No.	Chromosome	Number of polymorphisms	Number of genes	Genes	Number of references
1	6	756	135	ABHD16A   AGER   AIF1   APOM   ATAT1   ATF6B   ATP6V1G2-DDX39B   BAG6   BAK1   BRD2   BTNL2   C2   C6orf10   C6orf100   C6orf15   C6orf25   C6orf47   CCHCR1   CCR6   CD24   CFB   COL11A2   DAXX   DDR1   DDX39B   DHX16   DNAH8   DPCR1   DXO   EGFL8   EHMT2   ESR1   ETV7   FAM120B   GNL1   GPANK1   GPSM3   HCG17   HCG18   HCG22   HCG23   HCG26   HCG27   HCG9   HLA-A   HLA-B   HLA-C   HLA-DMA   HLA-DMB   HLA-DOA   HLA-DOB   HLA-DPA1   HLA-DPB1   HLA-DQA1   HLA-DQA2   HLA-DQB1   HLA-DQB2   HLA-DRA   HLA-DRB1   HLA-F   HLA-F-AS1   HLA-G   HSD17B8   HSPA1L   IL17A   IL17F   IP6K3   ITPR3   LEMD2   LINC00243   LOC100130476   LOC100294145   LOC101929072   LOC154449   LST1   LTA   LY6G5C   LY6G6C   LY6G6D   LY6G6F   MCCD1   MICA   MICB   MLN   MNF1   MSH5   MUC22   NCR3   NELFE   NFKBIE   NFKBIL1   NOTCH4   NRM   OFCC1   PBX2   PPP1R11   PPT2   PRDM1   PRL   PRRC2A   PSMB8   PSMB9   PSORS1C1   PSORS1C3   RING1   RIPK1   RNF39   RNF5   SAPCD1   SKIV2L   SLC44A4   SNORD84   SOD2   STK19   SUMO4   SYNGAP1   TAGAP   TAP1   TAP2   TAPBP   TCF19   TNF   TNFAIP3   TNXB   TPMT   TRIM10   TRIM15   TRIM26   TRIM31   TRIM40   VARS2   VEGFA   VPS52   ZNF391   ZNRD1-AS1	135
2	1	292	64	AMPD1   AP4B1   AP4B1-AS1   BCL2L15   C1QA   C1orf177   CD244   CD247   CD46   CD5L   CFH   CSMD2   FAM213B   FASLG   FCGR2A   FCGR2B   FCGR3A   FCGR3B   FCRL1   FCRL2   FCRL3   FCRL4   FCRL5   FOXJ3   GBP6   GPR137B   GSTM1   HEATR1   IKBKE   IL10   IL23R   IL6R   INADL   KAZN   LCE3C   LOC100506023   LOC100506929   MAGI3   MIR181A1HG   MMEL1   MTHFR   MTR   NCF2   NLRP3   PADI4   PARP1   PHTF1   PPAP2B   PSMB2   PTGS2   PTPN22   PTPRC   RCOR3   RSBN1   SELE   SLAMF6   SPRR2F   TACSTD2   TLR5   TNFRSF1B   TRIM67   UBE2Q1   VCAM1   VTCN1	197
3	2	234	45	ABCG5   ACP1   ADAM17   AFF3   AGFG1   APOB   ATIC   BCS1L   CD28   CERS6   CKAP2L   CTLA4   CTNNA2   DARS   FAM150B   GLS   HECW2   HSPD1   IAH1   ICOS   IFIH1   IL18R1   IL1A   IL1B   IL1F10   IL1R1   IL1RN   IL37   ITGAV   LINC01104   LINC01185   LOC100506047   NPAS2   PDCD1   PLB1   REL   SLC11A1   SPHKAP   SPRED2   STAT1   STAT4   TANK   TLK1   TTC7A   USP40	115
4	12	92	41	A2M   CD4   CD69   CLEC12A   CLEC4A   CLEC4C   CLEC4D   CLEC4E   CLEC6A   CLEC7A   CNPY2   ERBB3   GNB3   IFNG   IGF1   IRAK3   ITPR2   KIF5A   KLRC1   KLRC2   KLRC4-KLRK1   KLRK1   LINC01234   MANSC1   NAA25   NECAP1   OS9   P2RX7   RIC8B   SH2B3   SLCO1B1   SLCO1C1   STAT2   SVOP   SYT1   TMEM117   TNFRSF1A   TRHDE   UNG   VDR   ZNF705A	51
5	5	120	40	ACSL6   ADAMTS12   ADRB2   ANKRD55   ANXA6   ARL15   C5orf30   C5orf56   CD14   DHFR   DUSP1   HAVCR1   HAVCR2   IL12B   IL13   IL3   IL4   IL7R   IRF1   KIF3A   LEAP2   LMNB1   LOC101927705   MAP3K1   MIR146A   MTRR   NR3C1   NSD1   OSMR   PDLIM4   RAD50   RAPGEF6   RGS14   SEPT8   SLC22A4   SLC22A5   SPARC   SPOCK1   TIMD4   TNIP1	68
6	11	61	33	C11orf30   CAT   CYP2R1   DHCR7   ETS1   F2   GRAMD1B   GRM5   GSTP1   IGF2   IL18   MACROD1   MAML2   MMP1   MMP13   MMP3   MMP7   MTNR1B   NADSYN1   PDE3B   PHRF1   S100A11P3   SAA1   SCGB1A1   SERPING1   SHANK2   TIRAP   TRAF6   UBE4A   UCP2   UVRAG   VPS37C   WTAPP1	51
7	3	59	29	ADIPOQ   ARHGEF3   BRPF1   BTLA   CCR2   CCR5   CD80   CD86   CX3CR1   DNASE1L3   ERC2   FAM107A   FHIT   GHRL   GHSR   IL12A   LOC101927874   LOC152350   MBD4   MYD88   OGG1   PDZRN3   PLCL2   PPARG   PRICKLE2   PXK   TF   TLR9   VIPR1	45
8	4	64	27	ADAD1   ANAPC4   ATP10D   BANK1   ELOVL6   EMCN   FAM193A   FGB   GC   IL15   IL2   IL21   IL21-AS1   IL8   KIAA1109   NFKB1   PALLD   PPP3CA   RFC1   RNF175   SNCA   SPP1   TLR1   TLR10   TLR2   TLR3   TLR6	43
9	10	42	26	ADAMTS14   ANK3   ARID5B   CASP7   CELF2   CHUK   CUBN   CYP17A1   DKFZp667F0711   EGR2   FAS   GATA3   GPR123   HTRA1   IL2RA   LRRC18   MARCH8   MBL2   MYPN   NFKB2   NRG3   PLAU   RTKN2   SFTPD   TCF7L2   WDFY4	34
10	7	133	26	ABCB1   ATP6V0A4   CAV2   CCL24   CCL26   CDK6   CFTR   COL28A1   CPED1   EGFR   EXOC4   GSTK1   ICA1   IL6   IRF5   JAZF1   NOD1   NOS3   NPSR1   PODXL   PON1   PPP1R9A   SERPINE1   TMEM178B   TNPO3   TRBV3-1	72
11	19	53	25	APOC1   CARD8   CARM1   CD209   CEP89   DNASE2   FCAR   GDF15   GP6   ICAM1   ICAM3   IL12RB1   LDLR   LILRA4   MYO9B   NACC1   NFKBIB   NLRP2   RETN   SARS2   TGFB1   TYK2   XRCC1   ZFP36   ZNF302	41
12	9	109	21	ACTL7A   ALDH1A1   C5   C9orf72   CCL21   CD274   CDKN2B-AS1   CNTRL   FAM205A   FCN1   GNAQ   IKBKAP   IL33   LOC101929761   MOB3B   PDCD1LG2   PHF19   PTGES   TLR4   TRAF1   TRIM32	43
13	17	44	17	ABR   ACE   CCL11   CCL2   CCL5   FOXJ1   FOXN1   LOC101928122   MAP3K14   NLRP1   NOS2   OR1A1   SHMT1   SLC39A11   SOCS3   TBX21   TP53	28
14	20	34	15	ADA   CD40   DNMT3B   DTD1   GDF5   ITCH   ITPA   MMP9   MYH7B   PHACTR3   PLCB1   PTPRT   SLC12A5   SPINT4   ZGPAT	36
15	16	335	15	AMFR   CETP   CIITA   CLEC16A   COTL1   CYBA   DHODH   DNASE1   IL4R   ITGAM   MMP2   MPG   NOD2   SOCS1   SPNS1	40
16	22	40	13	ADORA2A   BCR   GATSL3   GRAMD4   GSTT1   HMOX1   IL2RB   LGALS2   MIF   NCF4   RAC2   SYNGR1   UBE2L3	27
17	8	30	11	BLK   CSMD1   EYA1   FAM167A   GGH   IKBKB   MSRA   NAT2   POLB   SFRP1   TNFRSF11B	14
18	13	23	10	BORA   CLYBL   DOCK9   GUCY1B2   HTR2A   KLF12   SLC10A2   SPATA13   TNFSF11   TNFSF13B	10
19	X	27	10	CD40LG   CYBB   FOXP3   HCFC1   IRAK1   MECP2   NAA10   TLR7   TLR8   TMEM187	12
20	21	15	8	ADAMTS1   AIRE   BRWD1   BRWD1-AS1   JAM2   RCAN1   RUNX1   UBASH3A	13
21	14	54	8	ESR2   INF2   LGALS3   MTHFD1   NFKBIA   PRKCH   RAD51B   RIN3	10
22	18	12	8	CD226   CTIF   DCC   IMPA2   LINC01254   MBP   PTPN2   TYMS	16
23	15	13	7	ACAN   ADAMTS7   CYP1A1   CYP1A2   RASGRP1   SEMA6D   VIMP	8
24	MT	2	2	COX2   CYTB	2

4 . Top 50 genes of positive

Table 2. The statistical information of top 50 genes in RADB (sorted by number of statistically significant references)

No.	Entrez Gene ID	Gene Symbol	Chromosome	Startloci	Endloci	References Total Stat. Significanta

1	26191	PTPN22	1	114356433	114414375	50	37
2	7124	TNF	6	31543344	31546113	41	23
3	6775	STAT4	2	191894302	192016322	29	21
4	1493	CTLA4	2	204732511	204738683	33	17
5	23569	PADI4	1	17634690	17690495	25	16
6	3586	IL10	1	206940948	206945839	20	10
7	2214	FCGR3A	1	161511549	161520413	12	8
8	3553	IL1B	2	113587337	113594356	17	8
9	7185	TRAF1	9	123664671	123691451	17	8
10	115352	FCRL3	1	157647978	157670647	15	8
11	3569	IL6	7	22766766	22771621	16	8
12	79258	MMEL1	1	2522081	2564481	13	7
13	4524	MTHFR	1	11845787	11866160	14	7
14	3663	IRF5	7	128577994	128590089	9	7
15	3565	IL4	5	132009678	132018370	12	7
16	7128	TNFAIP3	6	138188325	138204451	9	6
17	4855	NOTCH4	6	32162620	32191844	6	6
18	10665	C6orf10	6	32260475	32339656	5	5
19	56244	BTNL2	6	32362513	32374900	6	5
20	23534	TNPO3	7	128594234	128695227	9	5
21	3606	IL18	11	112013974	112034840	9	5
22	1235	CCR6	6	167525295	167552629	8	5
23	7040	TGFB1	19	41836812	41859831	12	5
24	4049	LTA	6	31539876	31542101	7	5
25	958	CD40	20	44746906	44758384	14	5
26	5966	REL	2	61108752	61150178	9	5
27	399716	DKFZp667F0711	10	6392283	6392831	10	4
28	84162	KIAA1109	4	123091758	123283914	6	4
29	3566	IL4R	16	27325230	27376099	6	4
30	7133	TNFRSF1B	1	12227060	12269277	11	4
31	6891	TAP2	6	32789610	32806547	7	4
32	5788	PTPRC	1	198608098	198726605	7	4
33	4795	NFKBIL1	6	31514628	31526606	6	4
34	5243	ABCB1	7	87133179	87342639	5	4
35	26147	PHF19	9	123617931	123639606	5	4
36	3559	IL2RA	10	6052657	6104333	8	4
37	10666	CD226	18	67530192	67624232	6	4
38	7189	TRAF6	11	36505317	36531863	7	4
39	4314	MMP3	11	102706528	102714342	5	4
40	150577	LINC01104	2	100824716	100867946	6	4
41	7919	DDX39B	6	31497996	31510252	4	4
42	7421	VDR	12	48235320	48298814	7	4
43	199	AIF1	6	31582994	31584798	4	4
44	90355	C5orf30	5	102594442	102614361	5	3
45	4261	CIITA	16	10971055	11018840	13	3
46	84868	HAVCR2	5	156512843	156536248	3	3
47	23274	CLEC16A	16	11038345	11276046	5	3
48	9374	PPT2	6	32121229	32131458	3	3
49	54665	RSBN1	1	114304454	114355070	5	3
50	326	AIRE	21	45705721	45718102	3	3

^a Stat. Significant : P value < 0.05 was considered significant.