Figure S1. First and second principal components of 1339 TRM

(1)

Figure S1. First and second principal components of 1339 TRM-like cells. Points within and out of the 95% confidence interval (dotted ellipse) are highlighted in green and red, respectively.

(2)

Figure S2. 2d density plot for CXCR6 expression vs pseudotime. The Pearson correlation coefficient correlation between CXCR6 and the cellular trajectory is -0.36, aligning with our finding that lower CXCR6 expression is correlated with severe COVID-19 symptoms.

Figure S3. Sequence logos representing DNA binding site generated from position weight matrix (PWM) for transcription factor RELA and SP1. In (a) and (b), the SNPs rs10490770 (T/C) and rs67959919 (G/A) were predicted to have the strongest impact on their sequence (GTGGATTTTCA - Reverse strand, p = 9.8 × 10^-4 and TACCCGCCGG - Reverse strand, p = 9.3 × 10^-4) by utilizing the RSAT online tool (Table S7). The polymorphism site within the transcription factor binding site is highlighted in the red box.

(3)

Figure S4. Violin plots showing the distribution of key features between moderate and severe patients. We calculated the proportion of the effector and naïve T cell markers expressed in each cell. The naïve markers include BCL2, SELL, KLF2, CCR7, TCF7, LEF1, ID3, BACH2, and IL7R. And the effector markers include GZMB, PRF1, IRF4, IFNG, TNFRSF9, PDCD1, LAG3, HAVCR2, TOX, and NR4A2. The median score of each category is on the top of each violin plot accordingly. The “*” on the third column denotes the naïve markers without SELL gene. The “TRM sig score” was calculated from the 31 TRM signature genes described in Methods.

The M and S represent moderate and severe patients, respectively.

(4)

Figure S5. LocusZoom views for two Host Genetics Initiates GWAS datasets in the 3p21.31 locus. In (a) and (b), the x-axis is the chromosome position in million base pairs (Mb) on GRCh37 reference genome and y-axis is the SNP –log10 (p-value) from the two GWASHGI

(5)

datasets (round 4 alpha and round 4 freeze). The color indicates the strength of linkage disequilibrium to the lead SNP rs35081325.

(6)

Table S1. TWAS S-PrediXcan MASHR model result in the 3p21.31 locus

Gene Symbol zscore pvalue best_gwas_p largest_weight Tissue Cohort

CXCR6 -8.525 1.53E-17 4.04E-21 0.193 Lung HGI

CCR9 6.502 7.90E-11 7.90E-11 0.14 Whole Blood HGI CCR9 6.263 3.78E-10 3.78E-10 0.14 Whole Blood SCGG

CCR3 -5.451 5.00E-08 5.00E-08 0.109 Spleen HGI

CXCR6 -4.186* 2.84E-05 4.66E-06 0.193 Lung SCGG

CCR5 -3.661 0.000252 0.00109 0.098 Lung SCGG

XCR1 3 0.0027 0.0027 0.229 Whole Blood SCGG

CCR5 -2.451 0.0142 0.00291 0.098 Lung HGI

FYCO1 2.425 0.0153 0.000862 0.158 Spleen HGI

FYCO1 2.336 0.0195 0.0163 0.216 Lung HGI

CCR2 2.098 0.0359 0.0359 0.089 Spleen HGI

CCR3 -2.09 0.0367 0.0367 0.109 Spleen SCGG

FYCO1 1.986 0.0471 0.0471 0.06 Whole Blood SCGG

CCR2 1.863 0.0625 9.60E-08 0.091 Lung HGI

CCR2 -1.862 0.0626 0.0479 0.091 Lung SCGG

FYCO1 1.862 0.0627 0.0471 0.158 Spleen SCGG

CXCR6 -1.85 0.0644 0.0639 0.125 Spleen HGI

FYCO1 1.671 0.0947 0.0471 0.216 Lung SCGG

CCR3 -1.556 0.12 0.0367 0.105 Lung SCGG

CCR1 -1.55 0.121 0.121 0.378 Whole Blood SCGG

CCR1 -1.55 0.121 0.121 0.179 Spleen SCGG

CCR1 -1.182 0.237 0.237 0.179 Spleen HGI

CCR1 -1.182 0.237 0.237 0.378 Whole Blood HGI

CCR2 -1.065 0.287 0.287 0.089 Spleen SCGG

CCRL2 -1.058 0.29 0.29 0.094 Lung HGI

CCRL2 -1.058 0.29 0.29 0.088 Spleen HGI

CCR3 -0.999 0.318 5.00E-08 0.105 Lung HGI

CCR5 0.903 0.366 0.366 0.152 Whole Blood HGI

CCR5 0.817 0.414 0.00204 0.066 Spleen SCGG

CCR2 0.757 0.449 0.162 0.082 Whole Blood HGI

XCR1 -0.714 0.475 0.475 0.131 Lung HGI

CCRL2 -0.623 0.533 0.533 0.094 Lung SCGG

CCRL2 -0.623 0.533 0.533 0.088 Spleen SCGG

CCR5 -0.515 0.606 0.254 0.066 Spleen HGI

FYCO1 0.472 0.637 0.637 0.06 Whole Blood HGI

XCR1 0.317 0.752 0.752 0.131 Lung SCGG

CXCR6 0.237 0.813 0.813 0.125 Spleen SCGG

(7)

CCR3 0.09 0.928 5.00E-08 0.282 Whole Blood HGI

XCR1 -0.005 0.996 0.996 0.229 Whole Blood HGI

SCGG: Severe COVID-19 GWAS Group; |z-score| > 4.56 indicates significant colocalization;

*indicates suggestive significance (|z-score| > 4.06).

Table S2. eCAVIAR colocalization posterior probability results in the 3p21.31 locus Gene symbol coloc_snp_id coloc_gwas_p CLPP Tissue/Cell lines Cohort

CXCR6 rs1994492 5.02E-22 0.785221 Lung HGI

CXCR6 rs1994492 5.02E-22 0.587253 Spleen HGI

CCR3 rs1994492 5.02E-22 0.582235 Spleen HGI

CCR1 rs35731912 1.25E-37 0.098346 TFH SCGG

FYCO1 rs35731912 1.25E-37 0.009921 TFH SCGG

CCR3 rs1994492 5.02E-22 0.009707 Lung HGI

LZTFL1 rs13081482 7.90E-11 0.008973 Lung HGI

XCR1 rs35731912 1.25E-37 0.006862 TFH SCGG

LZTFL1 rs73064425 1.37E-38 0.006572 TFH HGI

LZTFL1 rs35731912 1.25E-37 0.005747 TFH SCGG

CCR9 rs35731912 1.25E-37 0.004495 Monocytes HGI

CCRL2 rs73064425 1.37E-38 0.004444 TFH HGI

CCR3 rs35731912 1.25E-37 0.004102 TFH SCGG

CCR5 rs35731912 1.25E-37 0.004039 TFH SCGG

CCR9 rs1994492 5.02E-22 0.003966 Monocytes HGI

CCR5 rs1994492 5.02E-22 0.003926 TFH HGI

CCR3 rs1994492 5.02E-22 0.003751 TFH HGI

LZTFL1 rs35731912 1.25E-37 0.003747 Monocytes HGI

LZTFL1 rs1994492 5.02E-22 0.003509 Monocytes HGI

CCR3 rs73064425 1.37E-38 0.003362 TFH HGI

FYCO1 rs73064425 1.37E-38 0.002868 TFH HGI

CCRL2 rs35731912 1.25E-37 0.002867 TFH SCGG

CCR1 rs35731912 1.25E-37 0.002804 Monocytes HGI CCR9 rs13081482 3.78E-10 0.002578 Monocytes SCGG XCR1 rs35731912 1.25E-37 0.002508 Monocytes HGI

LZTFL1 rs1994493 3.36E-06 0.002401 TFH SCGG

CCR1 rs35731912 1.25E-37 0.002386 TFH HGI

LZTFL1 rs13081482 3.78E-10 0.002291 Monocytes SCGG

(8)

CCR5 rs1994493 3.36E-06 0.001977 TFH SCGG XCR1 rs13081482 3.78E-10 0.001948 Monocytes SCGG

CCR9 rs13081482 7.90E-11 0.001882 Lung HGI

FYCO1 rs1994492 5.02E-22 0.001861 TFH HGI

CCR1 rs13081482 7.90E-11 0.001796 Spleen HGI

CCR9 rs35731912 1.25E-37 0.001599 Monocytes SCGG CXCR6 rs13081482 7.90E-11 0.001587 Spleen HGI CCR1 rs13081482 3.78E-10 0.001567 Monocytes SCGG CXCR6 rs13081482 3.78E-10 0.001562 Monocytes SCGG

CXCR6 rs1994493 4.91E-22 0.001421 Spleen HGI

LZTFL1 rs35731912 1.25E-37 0.001322 Monocytes SCGG CCR2 rs13081482 7.90E-11 0.001314 Whole_Blood HGI

CCR2 rs35731912 1.25E-37 0.001259 TFH SCGG

CXCR6 rs35731912 1.25E-37 0.001227 Monocytes HGI XCR1 rs35731912 1.25E-37 0.001215 Monocytes SCGG FYCO1 rs13081482 7.90E-11 0.001138 Whole_Blood HGI

CCR9 rs35044562 6.10E-11 0.001109 Lung HGI

CCRL2 rs13081482 7.90E-11 0.001103 Whole_Blood HGI

XCR1 rs73064425 1.37E-38 0.001048 TFH HGI

CCR9 rs34326463 4.17E-39 0.001041 Lung HGI

CXCR6 rs35731912 1.25E-37 0.001026 Monocytes SCGG

TFH: T follicular helper cells; CLPP: colocalization posterior probability; HGI: Host Genetics Initiative; SCGG: Severe COVID-19 GWAS Group; CLPP > 0.1 indicates significant

colocalization

Table S3. fastENLOC regional colocalization probability results in the 3p21.31 locus

Gene SNP

SNP_gwas_

p RCP Tissue/ cell lines

Cohor t CXCR

6 rs3508132

5 2.49E-10 0.9986 TFH SCG

G CXCR

6 rs1771305

4 3.74E-10 0.9978 TFH SCG

G CXCR

6

rs3508132

5 3.82E-39 0.9972 TFH HGI

CXCR 6

rs1771305

4 8.51E-39 0.9933 TFH HGI

(9)

CCR5 rs7289367

1 1.55E-08 0.8811 Monocytes SCG

G CCRL

2 rs1771305

4 3.74E-10 0.5054 TFH SCG

G CCRL

2

rs1771305

4 8.51E-39 0.5031 TFH HGI

CCR5

rs6795991

9 2.62E-10 0.4985 Monocytes

SCG G CCR5

rs1307885

4 2.96E-10 0.4983 Monocytes

SCG G CCR5

rs7132508

8 2.94E-10 0.4983 Monocytes

SCG G CCR5

rs3562455

3 3.36E-10 0.4981 Monocytes

SCG G CCR5 rs1307885

4 7.45E-39 0.4927 Monocytes HGI

CCRL

2 rs1307885

4 2.96E-10 0.4927 TFH SCG

G CCR5

rs7132508

8 8.76E-39 0.4914 Monocytes HGI

CCR5

rs6795991

9 8.83E-39 0.4914 Monocytes HGI

CCR5

rs3562455

3 9.36E-39 0.4908 Monocytes HGI

CCRL 2

rs1307885

4 7.45E-39 0.4907 TFH HGI

CXCR 6

rs1771410

1 5.41E-07 0.3685 TFH

SCG G CXCR

6 rs6795991

9 2.62E-10 0.2497 TFH SCG

G CXCR

6 rs1307885

4 2.96E-10 0.2496 TFH SCG

G CXCR

6

rs7132508

8 2.94E-10 0.2496 TFH

SCG G CXCR

6

rs1307885

4 7.45E-39 0.2486 TFH HGI

CXCR 6

rs7132508

8 8.76E-39 0.2483 TFH HGI

CXCR 6

rs6795991

9 8.83E-39 0.2483 TFH HGI

CCR5 rs1771410

1 5.41E-07 0.229 Monocytes SCG

G CXCR

6 rs6808719

3 1.76E-06 0.1691 TFH SCG

G CXCR

6

rs3581448

8 1.77E-06 0.1683 TFH

SCG G

(10)

CXCR

6 rs1307575

8 2.19E-06 0.1436 TFH SCG

G CXCR

6 rs7628152

1 2.95E-06 0.114 TFH SCG

G CXCR

6

rs7132700

9 3.19E-06 0.1073 TFH

SCG G CXCR6

rs3461909

3 2.89E-06 0.09725 TFH SCGG

CXCR6

rs3516109

9 2.83E-06 0.08404 TFH SCGG

CXCR6

rs1307226

7 4.57E-06 0.08047 TFH SCGG

CXCR6

rs1309560

2 4.60E-06 0.08002 TFH SCGG

CXCR6 rs7132510

2 4.75E-06 0.06915 TFH SCGG

CXCR6 rs3528089

1 5.62E-06 0.0679 TFH SCGG

CXCR6

rs1306857

0 4.61E-06 0.06303 TFH SCGG

CXCR6 rs3851346 1.71E-06 0.04292 TFH SCGG CXCR6 rs1309317

9 4.91E-06 0.03791 TFH SCGG

CCR9 rs9824651 1.14E-05 0.03784 TFH SCGG

CXCR6 rs9824651 1.14E-05 0.03784 TFH SCGG

CCR9 rs9825081 1.16E-05 0.03729 TFH SCGG

CXCR6 rs9825081 1.16E-05 0.03729 TFH SCGG CXCR6 rs1309203

0 4.66E-06 0.03591 TFH SCGG

CXCR6

rs7132701

0 2.83E-06 0.02923 TFH SCGG

CXCR6

rs3476661

4 6.99E-06 0.02573 TFH SCGG

CXCR6

rs1308536

7 1.91E-05 0.02438 TFH SCGG

CXCR6

rs1306363

5 1.91E-05 0.02435 TFH SCGG

CXCR6 rs1994492 3.36E-06 0.0216 TFH SCGG

CCRL2 rs7616942 1.74E-01 0.02076 TFH SCGG CXCR6

rs3546422

1 1.20E-05 0.01807 TFH SCGG

CCR5 rs1776374

2 1.19E-09 0.01686 Monocytes SCGG

CXCR6 rs1308955

4 4.61E-06 0.01294 TFH SCGG

(11)

CXCR6 rs3542056

5 4.26E-06 0.01222 TFH SCGG

CXCR6 rs3404791

5 4.29E-06 0.01216 TFH SCGG

CXCR6

rs1306841

0 6.27E-05

0.00890

4 TFH SCGG

CCR5

rs5587532

8 1.29E-06

0.00860

5 Monocytes SCGG CXCR6

rs1306463

2 6.82E-05

0.00829

2 TFH SCGG

CCR9

rs1306974

2 2.14E-05

0.00737

8 TFH SCGG

CCRL2 rs7616942 7.83E-01 0.00725 TFH HGI

CCR9 rs9877748 2.21E-05 0.00718 TFH SCGG

CCR9 rs9845382 2.28E-05

0.00700

1 TFH SCGG

CXCR6 rs3511086

4 4.99E-06 0.00694

9 TFH SCGG

CCR5 rs6780028 1.80E-06 0.00658

9 Monocytes SCGG CCR5 rs2088692 1.96E-06

0.00615

3 Monocytes SCGG CCRL2

rs3425498

7 6.34E-05

0.00441

1 TFH SCGG

CXCR6

rs1309674

1 4.27E-06

0.00428

2 TFH SCGG

CCRL2

rs1306463

2 6.82E-05

0.00414

6 TFH SCGG

CXCR6

rs1721598

1 4.47E-06

0.00412

6 TFH SCGG

CXCR6 rs3486357

5 4.53E-06 0.00408

3 TFH SCGG

CXCR6 rs3434058

7 4.63E-06 0.00401

2 TFH SCGG

CXCR6

rs3409327

1 4.89E-06

0.00383

6 TFH SCGG

CXCR6

rs3446058

7 4.93E-06

0.00381

2 TFH SCGG

CXCR6

rs3445200

2 4.95E-06

0.00380

1 TFH SCGG

CCR9 rs9845542 1.79E-04 0.00368 TFH SCGG

CCR1 rs7613489 3.31E-01

0.00329

1 TFH SCGG

CCR9

rs3508132

5 3.82E-39

0.00187

7 WholeBlood HGI

(12)

CCR9 rs3432646

3 4.17E-39 0.00173 WholeBlood HGI

CCR1 rs7613489 5.84E-01 0.00172

1 TFH HGI

CCR9

rs1308148

2 3.78E-10

0.00165

5 WholeBlood SCGG CCR5 rs9990063 2.70E-04

0.00133

1 Monocytes SCGG CCR9

rs3428807

7 6.02E-39

0.00121

6 WholeBlood HGI CCR9

rs3550862

1 6.32E-39

0.00116

rs3504456

2 4.81E-10

0.00111

6 WholeBlood SCGG CCR9 rs3565289

9 2.59E-10 0.00108

1 WholeBlood SCGG CCRL2 rs6773335 8.65E-04 0.00100

8 TFH SCGG

CCR5 rs1488371 3.89E-04

0.00098

rs3550862

1 2.31E-10

0.00082

3 WholeBlood SCGG CCR5

rs3490604

3 4.86E-04 0.00082 Monocytes SCGG

CCR9

rs3508132

5 2.49E-10

0.00076

rs3573191

2 1.91E-10

0.00068

4 WholeBlood SCGG CCR9 rs3428807

7 3.14E-10 0.00062 WholeBlood SCGG

CCR9 rs3432646

3 3.45E-10 0.00056

rs7306442

5 2.94E-10

0.00056

rs7306442

5 1.37E-38

0.00047

8 WholeBlood HGI CCR5 rs9834860 6.02E-04

0.00046

rs1308228

0 1.00E-03

0.00045

7 Monocytes SCGG CCR5 rs1343402

9 1.01E-03 0.00045

3 Monocytes SCGG CCR5 rs1602579 1.04E-03 0.00044

0.00044

2 Monocytes SCGG

(13)

CCR5 rs1306573

7 1.07E-03 0.00043

0.00040

0.00038

0.00036

rs5752795

4 5.95E-04

0.00034

8 Monocytes SCGG CCR9 rs1307885

4 7.45E-39 0.00031

2 WholeBlood HGI CCR1 rs5745986

4 5.13E-01 0.00028

2 TFH SCGG

CCR9

rs1771305

4 8.51E-39

0.00027

rs7770711

6 1.98E-01

0.00025

7 TFH SCGG

CCR9

rs3562455

3 9.36E-39

0.00025

rs6795991

9 8.83E-39

0.00024

rs7132508

8 8.76E-39

0.00023

9 WholeBlood HGI CCR5 rs5952141

5 9.84E-04 0.00023

1 TFH SCGG

CCR5 rs7646264 1.11E-03 0.00021 Monocytes SCGG CCR9

rs6795991

9 2.62E-10

0.00020

9 WholeBlood SCGG CXCR6 rs4493469 5.24E-03 0.00020

8 TFH SCGG

CCR9 rs1307885

4 2.96E-10 0.00020

6 WholeBlood SCGG CCR5 rs6805094 1.16E-03

0.00020

rs7637445

9 6.76E-10

0.00019

rs7132508

8 2.94E-10

0.00018

5 WholeBlood SCGG CCR9 rs3562455 3.36E-10 0.00018 WholeBlood SCGG

(14)

3 3 CCR9

rs1771305

4 3.74E-10

0.00016

rs5745986

4 9.54E-01

0.00015

9 TFH HGI

CCR1 rs6763438 3.77E-01

0.00015

7 TFH HGI

XCR1

rs7132700

6 2.77E-06

0.00013

9 TFH SCGG

CCR9 rs1306596

4 1.49E-02 0.00011

4 TFH SCGG

CXCR6

rs1051074

9 1.58E-02

0.00010

9 TFH SCGG

CCR9

rs3487015

9 1.77E-02

0.00010

1 TFH SCGG

TFH: T follicular helper cells; RCP: regional colocalization probability; HGI: Host Genetics Initiative; SCGG: Severe COVID-19 GWAS Group; RCP > 0.1 indicates significant

colocalization

Table S4. Sample composition of TRM cells and mean expression of CXCR6 in each sample

Sample ID

Sample ID group

Severe or moderate

Cell number in TRM cells

Mean expression of CXCR6 by sample

Proportion in CD8+ TRM cells

C141 O1 Moderate 343 1.44 0.31

C142 O2 Moderate 347 1.41 0.31

C144 O3 Moderate 75 1.49 0.068

C143 C1 Severe 144 1.05 0.13

C148 C3 Severe 31 0.86 0.028

C149 C4 Severe 26 1.23 0.023

C152 C5 Severe 62 0.55 0.056

C145 S1 Severe 73 0.36 0.066

Table S5. Hallmark pathways and their relevance scores.

Hallmark pathway Relevance score

INTERFERON_GAMMA_RESPONSE 0.630

ALLOGRAFT_REJECTION 0.569

APOPTOSIS 0.423

(15)

HYPOXIA 0.387

COMPLEMENT 0.359

P53_PATHWAY 0.283

ESTROGEN_RESPONSE_LATE 0.235

MTORC1_SIGNALING 0.218

GLYCOLYSIS 0.187

TNFA_SIGNALING_VIA_NFKB 0.186

G2M_CHECKPOINT 0.182

XENOBIOTIC_METABOLISM 0.175

INTERFERON_ALPHA_RESPONSE 0.146

ESTROGEN_RESPONSE_EARLY 0.119

ANDROGEN_RESPONSE 0.110

INFLAMMATORY_RESPONSE 0.075

MYC_TARGETS_V1 0.056

UNFOLDED_PROTEIN_RESPONSE 0.053

IL2_STAT5_SIGNALING 0.034

EPITHELIAL_MESENCHYMAL_TRANSITIO

N 0.029

OXIDATIVE_PHOSPHORYLATION 0.013

PROTEIN_SECRETION 0.010

PI3K_AKT_MTOR_SIGNALING 0.007

DNA_REPAIR -0.001

ADIPOGENESIS -0.005

CHOLESTEROL_HOMEOSTASIS -0.009

HEME_METABOLISM -0.014

IL6_JAK_STAT3_SIGNALING -0.016

MITOTIC_SPINDLE -0.025

UV_RESPONSE_UP -0.040

KRAS_SIGNALING_UP -0.054

UV_RESPONSE_DN -0.056

FATTY_ACID_METABOLISM -0.061

E2F_TARGETS -0.093

MYC_TARGETS_V2 -0.108

WNT_BETA_CATENIN_SIGNALING -0.113

TGF_BETA_SIGNALING -0.124

APICAL_JUNCTION -0.126

KRAS_SIGNALING_DN -0.143

COAGULATION -0.149

PEROXISOME -0.162

SPERMATOGENESIS -0.165

MYOGENESIS -0.165

(16)

REACTIVE_OXYGEN_SPECIES_PATHWAY -0.166

BILE_ACID_METABOLISM -0.214

Table S6. Transcription factors and their relevance scores.

Transcription factor Relevance score

RELA 0.495

NFKB1 0.383

MYC 0.317

USF1 0.297

SP1 0.216

MYCN 0.193

STAT1 0.186

CIITA 0.133

HDAC1 0.132

USF2 0.108

TWIST2 0.105

IRF1 0.091

CEBPB 0.076

ETS1 0.065

RFX5 0.062

YY1 0.050

TWIST1 0.037

PPARG 0.019

ATF4 0.005

HIF1A -0.011

XBP1 -0.019

AR -0.024

SP3 -0.033

FOS -0.036

JUN -0.037

ESR1 -0.038

BRCA1 -0.043

CREM -0.044

EP300 -0.055

RUNX1 -0.075

ATM -0.077

STAT3 -0.093

EGR1 -0.098

TP53 -0.099

BCL6 -0.105

(17)

E2F1 -0.109

WT1 -0.110

CREB1 -0.111

SPI1 -0.111

SIRT1 -0.125

DNMT1 -0.136

NR3C1 -0.137

TFAP2A -0.164

HSF1 -0.169

RUNX3 -0.180

(18)

ac_motif var_id CHR POS REF ALT p Beta SE var_class var_coord best_w worst_w w_diff best_pval worst_pval pval_ratio best_variant worst_variant best_offset worst_offset min_offset_diff best_strand worst_strand str_change best_seq worst_seq minor_allele_freq TF

M02921_2.00 rs71325088 3 45862952 T C 8.76E-39 7.01E-01 5.38E-02 SNV 3:45862951-45862952_+ 4.62 -0.92 5.53 0.00085 0.014 16.47 C T -7 -7 0 D D 0 ACAACACCTAG ACAACACTTAG 0.039486 SP1

M08006_2.00 rs10490770 3 45864732 T C 9.54E-39 7.01E-01 5.38E-02 SNV 3:45864731-45864732_+ 3.68 -2.31 6 0.00098 0.014 14.29 C T -10 -10 0 R R 0 GTGGATTTTCA ATGGATTTTCA 0.039486 RELA

M10294_2.00 rs67959919 3 45871908 G A 8.83E-39 7.01E-01 5.38E-02 SNV 3:45871907-45871908_+ 5.29 -1.64 6.93 0.00093 0.036 38.71 G A -2 -2 0 R R 0 TACCCGCCGG TACCCGCTGG 0.039486 SP1

Table S7. Predicted transcription factors (SP1 and RELA) bind affinity alterations on genome-wide significant SNPs in locus 3p21.31.

#column content

ac_motif: Accession number of the positions-pecific scoring matrix in Homo Sapien CIS-BP 2.0 var_id: SNP ID of the variation

CHR: chromosome in GRCh37 POS: position in GRCh37 REF: reference allele ALT:alternative allel

p: HGI round 4 alpha pvalue Beta: Beta coefficient SE: Standard error of Beta

var_class: Variation type, according to SNP Ontology (SO) nomenclature var_coord: Coordinates of the variation

best_w: Best weigth for the putative site worst_w: Worst weigth for the putative site

(19)

w_diff: Difference between best and worst weigth best_pval: P_value of the best putative site

worst_pval: P_value of the worst putative site

pval_ratio: Ratio between worst and best pval ( pval_ratio = worst_pval/best_pval ) best_variant: Variant in the best putative site

worst_variant: Variant in the worst putative site best_offest: Offset of the best putative site worst_offset: Offset of the worst putative site

min_offset_diff: Difference minimal between best and worst putative site best_strand: Strand of the best putative site (D:forward strand, R:reverse strand) worst_strand: Strand of the worst putative site (D:forward strand, R:reverse strand) str_change: Indicate if strand have change between the offset of min_offset_diff best_seq: Sequence of the worst putative site

worst_seq: Sequence of the worst putative site minor_alle_freq: Minor allele frequency

TF: the corresponding Transcriptional Factor of ac_motif