Supplementary Table 1. Characteristics of each study population
Netherlandsa
UKc
Spainc, d
Greekc
754
856
232
290
age in yrs (sd)
59.1 (7.5)
69 (na)
68.4 (9.1)
62.0 (12.8)
BMI in kg/m2
25.6 (3.6)
na
na
25.6 (3.4)
57%
46%
39%
58%
381
1737
740
278
60 (7.5)
65 (na)
67 (8.3)
66 (8.8)
82%
60%
75%
89%
27 (4.7)
Na
na
29.6 (4.6)
Hip
113
1290
257
52
Knee
161
447
261
226
Hip and/or knee
230
1737
518
278
Hand
223
na
222
na
study
controls
Female
casesa
agec in yrs (sd)
Female
BMI in kg/m2
a
The GARP study consists of 190 sibling pairs concordant for clinical and radiographically
confirmed OA (Kellgren and Lawrence ≥ 2) (1) at two or more joint sites of the hand, spine
(cervical or lumbar), knee or hip. bCases included from the UK, Spanish and Greek studies have
severe primary OA and had undergone a total knee replacement (TKR) or total hip replacement
(THR). c The hand OA patients included in the Spanish cohort were defined by clinical American
College of Rheumatology (ACR) criteria.(2) dOverall number of cases and controls available for
each study. eAge refers to age at recruitment (Netherlands, Spain and all controls) or joint
replacement (UK cases). BMI = body mass index, na = not available.
(1) Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis 1957; 16(4):494-502.
1
(2) Altman R, Alarcon G, Appelrouth D, Bloch D, Borenstein D, Brandt K et al. The American College of
Rheumatology criteria for the classification and reporting of osteoarthritis of the hand. Arthritis Rheum 1990;
33(11):1601-1610.
2
Supplementary Table 2: Location and minor allele frequency of the selected SNPsa
Gene
SNP
Chrom Location
MAF
(bp)
DIO3
Risk
Power (%)b Remarks
allele
rs1190715
14
101092832
0.48
C
95
Intron, hapmap
rs8011440
14
101094911
0.38
T
94
Intron, hapmap
rs945006
14
101099030
0.11
G
49
3'UTR
rs1378640
2
219625876
0.24
C
85
Hapmap located at 3' end of the gene
rs3731881
2
219628656
0.35
A
93
3' UTR
rs3731878
2
219628809
0.10
T
45
3'UTR
rs3100776
2
219629444
0.04
C
13
Intron, hapmap
rs1568400
17
35474634
0.26
C
87
Intron, hapmap
rs939348
17
35485379
0.26
T
87
Intron, hapmap
rs3744805
17
35501880
0.11
A
49
Intron, hapmap
USP33 rs12030080
1
77970910
0.06
A
23
Intron, hapmap
rs12121287
1
77974477
0.11
A
49
Coding non-synonymous
rs11162380
1
77975329
0.27
C
88
r2=0.8 with rs2296227 non-
IHH
THRA
synonymous SNP
rs2147318
1
78015226
0.25
G
86
r2=1 with rs12142671 nonsynonymous SNP
WSB1
a
rs4795552
17
22637508
0.40
A
94
Hapmap located at 5' end of the gene
rs7213148
17
22663173
0.03
T
9
Intron, hapmap
rs6505204
17
22668196
0.43
G
95
Intron, hapmap
Tagging SNPs were selected from HapMap Public Release #19 applying the efficient multi-marker
method with r2 > 0.8 and minor allele frequency (MAF) > 0.05 as implemented in the HapMap web
browser (http://www.hapmap.org;). SNP selector is a SNP selection tool build upon the high-quality SNP
database (HQSNP) developed by CHG bioinformatics group
http://snpselector.duhs.duke.edu/hqsnp36.html). It generates a SNP list sorted by tag SNP in LD block,
SNP quality, SNP function, SNP regulatory potential, and SNP mutation risk. UTR=untranslated region. b
Power determined at an alpha level of 0.0029 (0.05/number of SNPs measured), population risk
0.092, a log-additive or allelic model and an OR of 1.2.
3
Supplementary Table 3 Amount of alleles captured by the SNP selection
Gene
SNP
Capture
DIO3
rs1190715
The 3 SNPs genotyped capture all (100%)
rs8011440
alleles of DIO3 at r2 >= 0.8 and MAF 0.05
rs945006
IHH
rs1378640
The 4 SNPs genotyped capture 7 out of 9
rs3731881
(78%) alleles of IHH at r2 >= 0.8 and MAF
rs3731878
0.05
rs3100776
THRA
rs1568400
The 3 SNPs genotyped 5 out of 11 (45%)
rs939348
alleles of THRA at r2 >= 0.8 and MAF 0.05
rs3744805
USP33
rs12030080
The 4 SNPs genotyped capture 15 out of 23
rs12121287
(65%) alleles of USP33 at r2 >= 0.8 and MAF
rs11162380
0.05
rs2147318
WSB1
rs4795552
The 3 SNPs genotyped capture 10 out of 20
rs7213148
(50%) alleles of WSB1 at r2 >= 0.8 and MAF
rs6505204
0.05
MAF=minor allele frequency.
4