Skip to main content
. 2021 Dec 2;11:23292. doi: 10.1038/s41598-021-01324-0

Table 2.

Genetic association of SS-meQTLs and SS-eQTLs with SS and other related SADs mediated by DNA methylation or gene expression changes.

CpG Gene rsID SNP Position (hg38 Chr:bp) A1/A2 βmeQTL PmeQTL βEWAS P EWAS OR P PRECISESADSSADs
A. Genetic effects on SS mediated by changes in DNA methylation
cg08099136 PSMB8 rs9275569 6:32,710,259 C/T  − 0.018 1.92 × 10−04  − 0.062 2.43 × 10–09 2.03 1.57 × 10−08 SLE (1 x 10–04)
cg14880222 IFI44 rs1051047* 1:78,663,909 A/G 0.027 5.94 × 10−08  − 0.036 3.61 × 10–09 0.54 0.0127 SLE (0.042)
cg03879629 intergenic (CCR cluster) rs9838739* 3:46,095,597 T/C  − 0.046 5.21 × 10−05  − 0.071 7.81 × 10–09 1.71 0.0242 SLE (0.002), MCTD (0.008), UCTD (0.004)
cg12013713 PARP12 rs6962291*# 7:139,971,218 T/A  − 0.017 2.96 × 10−05  − 0.048 8.54 × 10–09 1.32 0.0270
Transcript Gene rsID SNP Position (hg38 Chr:bp) A1/A2 βeQTL PeQTL βdiffexp P diffexp OR P PRECISESADS
B.Genetic effects on SS mediated by changes in gene expression
ENSG00000166278 C2 rs1054684$# 6:32,809,044 T/C 0.300 3.57 × 10−04 0.911 1.46 × 10−13 4.04 2.16 × 10−13 SLE(1 x 10–05), MCTD (0.03), UCTD (0.048)
ENSG00000204267 TAP2 rs4947258 6:32,779,625 A/G 0.168 3.51 × 10−04 0.478 2.31 × 10−17 3.53 2.90 × 10−12 SLE(1 x 10–05)
ENSG00000240065 PSMB9 rs3117106 6:32,375,492 T/C 0.139 2.19 × 10−04 0.287 1.12 × 10−08 2.22 1.23 × 10−07 SLE (0.001)
ENSG00000204713 TRIM27 rs2523425* 6:29,526,364 C/T  − 0.069 9.24 × 10−06  − 0.136 1.06 × 10−06 1.51 7.32 × 10−04 SADSnoSS (0.03)
ENSG00000128604 IRF5 rs4731531$* 7:128,922,493 G/A 0.084 3.45 × 10−04 0.192 6.48 × 10−07 1.46 0.0014 SLE (0.005)
ENSG00000174444 RPL4 rs4482223 15:65,828,392 A/G 0.101 3.18 × 10−04  − 0.195 1.01 × 10−09 0.53 0.0019 RA (0.004)
ENSG00000124508 BTN2A2 rs3799378*# 6:26,404,046 A/G 0.096 2.74 × 10−04 0.228 4.61 × 10−08 1.54 0.0025
ENSG00000234127 TRIM26 rs9261518 6:30,149,108 G/A  − 0.113 2.66 × 10−05 0.154 3.65 × 10−09 0.60 0.0029 UCTD (0.01)
ENSG00000175970 UNC119B rs10849822* 12:120,939,591 G/C  − 0.066 3.28 × 10−04  − 0.161 2.88 × 10−09 1.48 0.0075 SLE (0.02)
ENSG00000162614 NEXN rs6660288 1:78,927,603 G/A 0.143 2.73 × 10−04 0.685 3.02 × 10−14 1.36 0.0156 MCTD (0.04), UCTD (0.02)
ENSG00000002549 LAP3 rs57570581 4:17,705,638 G/A  − 0.216 2.76 × 10−05 0.867 2.61 × 10−22 0.75 0.0187 UCTD (0.02)
ENSG00000204516 MICB rs9348883# 6:32,390,672 T/A  − 0.174 3.12 × 10−04 0.242 1.19 × 10−09 0.46 0.0276
ENSG00000154451 GBP5 rs76397273* 1:89,333,021 A/G  − 0.288 9.70 × 10−05 0.701 2.54 × 10−13 0.67 0.0301 SSc (0.007), UCTD (0.03)
ENSG00000184898 RBM43 rs289953 2:151,143,385 T/C 0.183 8.55 × 10−09 0.378 5.03 × 10−12 1.29 0.0398 SLE (0.03), SSc (0.01)
ENSG00000166750 SLFN5 rs11080327* 17:35,244,427 G/A 0.222 4.68 × 10−14 0.255 1.11 × 10−06 1.28 0.0401 PAPs (0.04)

Alleles represent major allele first, and then the minor allele, which is the allele tested in each analysis.

β meQTL represents the DNA methylation change with the increased in dosage of the minor allele.

P meQTL corresponds to the P value from the linear regression model that regresses out the number of minor alleles for a given SNP to DNA methylation levels adjusting by age, sex, batch effects, estimated cell proportions, disease status and first genetic component.

βEWAS represents the DNA methylation difference between SS and healthy controls from the epigenome-wide association study together obtained by linear regression model in which DNA methylation levels are regressed out by SS status and adjusted by age, sex, batch effects and estimated cell proportions.

OR represents the Odd Ratio obtained from genetic association testing based on logistic regression modeling which the SS statuts is regressed out by number of minor alleles for a given SNP adjusted by age, sex, batch effects, estimated cell proportions and first genetic component and its corresponding.

P represents the P-value obtained in the genetic associations.

SAD (OR, P) represents the odd ratio and P value obtained in genetic testing for other diseases. RA = Rheumatoid Arthritis, SLE = Systemic Lupus Erythemathosus, UCTD = Undifferentiated Connective Tissue Disease, SSc = Systemic Scleroderma, PAPs = Primary anti-phospholipid syndrome. SADSnoSS = All SADs patients excluding SS.

Genomic positions are based on the hg19 human reference sequence build (GRCh37).

* eQTL reported in GTEx project (https://www.gtexportal.org/home/), in the case of eQTL the same SNP-gene is reported.

# SNP associated with related disease phenotype in GWAS catalog (https://www.ebi.ac.uk/gwas/) or Open Target Genetics Portal (https://genetics.opentargets.org/).