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. Author manuscript; available in PMC: 2022 Mar 1.
Published in final edited form as: J Allergy Clin Immunol. 2020 Aug 11;147(3):894–909. doi: 10.1016/j.jaci.2020.07.030

TABLE II.

Genetic association and eQTL results of 48 GWAS-identified SNPs associated with expression levels of PGAP3, GSDMB, or GSDMA in the longitudinal cohort

SNP Position (hg38) SNP Type Gene Allelet‡ Associated Trait** LD†† (NHW) LD†† (AA) Asthma Severity*** Number of Exacerbations in 3 years††† eQTL of SARP3 in BEC (n=114) eQTL of GTEx database Lung Tissue (n=383)
Effect Allele OR P β P PGAP3 β (P) GSDMB β (P) GSDMA β (P)
rs2941504* 39674647 synonymous PGAP3 A/G Asthma2; eQTL for PGAP33 1 1 A 1.05 0.64 0.97 0.011 0.77 (5E-9) 0.30 (0.03) −0.32 (0.02) A ~ PGAP3↑ (2E-10); ORMDL3↑ (1E-7); GSDMA↓ (4E-6)
rs2517955* 39687428 intronic PGAP3 C/T eQTL for ORMDL34 C 1.10 0.35 1.05 0.0034 0.56 (5E-6) 0.28 (0.03) −0.11 (0.4) C ~ PGAP3↑ (1E-12); ORMDL3↑ (2E-6)
rs2952156*† 39720582 intronic ERBB2 A/G Asthma5 2 A 1.06 0.56 0.99 0.0081 0.76 (4E-8) 0.30 (0.04) −0.33 (0.02) A ~ PGAP3↑ (4E-10); ORMDL3↑ (4E-9); GSDMA↓ (7E-6); GSDMB↑ (2E-5)
rs4252665† 39729130 intronic ERBB2 T/C SLE31 T 0.69 0.15 −0.40 0.69 −0.02 (1.0) 0.04 (0.9) −0.28 (0.5) NS
rs2941522† 39754115 intergenic GRB7-IKZF3 T/C Asthma6 T 1.24 0.028 0.84 0.019 0.45 (8E-4) 0.33 (0.02) −0.54 (6E-5) T ~ GSDMB↑ (3E-15); ORMDL3↑ (4E-15); GSDMA↓ (1E-6); PGAP3↑ (1E-6)
rs12946510† 39756124 integenic GRB7-IKZF3 T/C UC32–33; CD32–33; MS34; IBD32–33,35 2 T 0.86 0.12 −0.72 0.046 −0.43 (0.002) −0.43 (0.002) 0.44 (0.002) T ~ GSDMB↓ (2E-9); ORMDL3↓ (9E-9); GSDMA↑ (1E-6)
rs2941509† 39764941 3′ UTR IKZF3 A/G SLE36–37 A 0.81 0.44 0.46 0.65 −0.08 (0.7) 0.04 (0.9) 0.02 (0.9) A ~ GSDMB↓ (3E-5)
rs907092*† 39766006 synonymous IKZF3 G/A A/G Asthma7–8; PBCh38 G 1.24 0.027 0.66 0.069 0.47 (8E-4) 0.50 (4E-4) −0.43 (0.003) G ~ GSDMB↑ (2E-9); ORMDL3↑ (5E-9); GSDMA↓ (2E-7)
rs10445308† 39781794 intronic IKZF3 C/T Atopy27 C 1.23 0.033 0.76 0.034 0.47 (7E-4) 0.51 (2E-4) −0.45 (1E-3) C ~ GSDMB↑ (7E-10); ORMDL3↑ (3E-9); GSDMA↓ (3E-8)
rs12450323† 39816455 intronic IKZF3 T/G Asthma9 T 1.15 0.24 0.96 0.023 0.63 (2E-4) 0.43 (0.01) 0.13 (0.4) T ~ ORMDL3↑ (1E-5); GSDMB↑ (2E-5); PGAP3↑ (2E-5)
rs9303277*† 39820216 intronic IKZF3 T/C PBCh39–42; SS43; SLE43 T 0.79 0.017 −0.84 0.017 −0.48 (4E-4) −0.40 (0.004) 0.49 (3E-4) T ~ GSDMB↓ (7E-15); ORMDL3↓ (6E-14); GSDMA↑ (2E-7); PGAP3↓ (7E-6)
rs143123127† 39850937 intronic IKZF3 A/G SLE37 A 0.80 0.43 −0.38 0.73 −0.02 (1.0) 0.30 (0.5) −0.77 (0.06) NA
rs9635726† 39863888 intronic IKZF3 C/T PBCh44 C 0.88 0.27 −1.14 0.0078 −0.63 (1E-4) −0.47 (0.005) −0.07 (0.7) C ~ GSDMB↓ (1E-5); ORMDL3↓ (2E-5); PGAP3↓ (2E-5)
rs4795397† 39867492 intergenic IKZF3-ZPBP2 A/G (G/A) Asthma8 IBD33 A 1.17 0.027 0.81 0.022 0.40 (0.003) 0.52 (1E-4) −0.42 (0.002) A ~ ORMDL3↑ (4E-9); GSDMA↓ (2E-8); GSDMB↑ (7E-8)
rs11655198† 39869916 intronic ZPBP2 (C/T) Asthma10 3 C 1.29 0.0097 0.82 0.019 0.40 (0.003) 0.44 (0.001) −0.30 (0.03) C ~ GSDMB↑ (6E-15); ORMDL3↑ (8E-12); GSDMA↓ (8E-7); PGAP3↑ (3E-6)
rs12936231* 39872867 intronic ZPBP2 (C/G) ORMDL3 promoter11 C 1.29 0.0089 0.87 0.013 0.40 (0.004) 0.42 (0.002) −0.37 (0.008) C ~ GSDMB↑ (5E-15); ORMDL3↑ (1E-14); GSDMA↓ (1E-7); PGAP3↑ (8E-6)
rs59716545† 39875604 intronic ZPBP2 (G/T) RA45 G 0.82 0.042 −0.89 0.012 −0.38 (0.005) −0.52 (1E-4) 0.31 (0.02) NA
rs12939457† 39875935 intronic ZPBP2 T/C Allergic rhinitis28 T 1.21 0.054 0.90 0.011 0.44 (0.002) 0.50 (3E-4) −0.40 (0.004) NA
rs35736272† 39876427 intronic ZPBP2 (C/T) AD46 C 0.81 0.033 −0.89 0.012 −0.40 (0.003) −0.53 (6E-5) 0.35 (0.01) C ~ ORMDL3↓ (7E-10); GSDMB↓ (3E-9); GSDMA↑ (4E-9);
rs12232497† 39883866 intergenic ZPBP2-GSDMB C/T AD47 C 0.81 0.033 −0.89 0.012 −0.40 (0.003) −0.53 (6E-5) 0.35 (0.01) C ~ ORMDL3↓ (7E-10); GSDMA↑ (3E-9); GSDMB↓ (3E-9)
rs2872507† 39884510 intergenic ZPBP2-GSDMB A/G RA48–49; T1D50; UC51; CD52–53 A 0.81 0.035 −0.89 0.012 −0.42 (0.002) −0.51 (2E-4) 0.35 (0.01) A ~ ORMDL31 (3E-10); GSDMB 1 (5E-10); GSDMA1 (2E-9)
rs12936409† 39887396 intergenic ZPBP2-GSDMB T/C RA48,54 T 0.81 0.030 −0.88 0.014 −0.43 (0.002) −0.52 (1E-4) 0.36 (0.009) T ~ ORMDL3↓ (8E-10); GSDMA↑ (4E-9); GSDMB↓ (9E-9)
rs8067378† 39895095 intergenic ZPBP2-GSDMB G/A PBCi55 G 0.76 0.0054 −0.88 0.011 −0.43 (0.002) −0.42 (0.003) 0.36 (0.01) G ~ GSDMB↓ (5E-15); ORMDL3↓ (1E-14); GSDMA↑ (1E-7); PGAP3↓ (8E-6)
rs12453507† 39896954 intergenic ZPBP2-GSDMB (G/C) T1D56 G 0.76 0.0050 −0.78 0.024 −0.36 (0.007) −0.43 (1E-3) 0.29 (0.03) G ~ GSDMB↓ (2E-15); ORMDL3↓ (2E-12); GSDMA↑ (2E-8); PGAP3↓ (1E-6)
rs8069176*† 39900944 intergenic ZPBP2-GSDMB G/A Asthma5 G 1.26 0.020 0.86 0.015 0.39 (0.003) 0.57 (9E-6) −0.33 (0.01) G ~ ORMDL3↑ (6E-11); GSDMA↓ (1E-10); GSDMB↑ (2E-10)
rs4795399† 39905186 intronic GSDMB T/C Asthma12†13 T 1.26 0.019 0.88 0.013 0.35 (0.007) 0.55 (2E-5) −0.31 (0.02) T ~ ORMDL3↑ (1E-10); GSDMA↓ (2E-10); GSDMB↑ (7E-10)
rs2305480*† 39905943 missense GSDMB G/A A/G Asthma14–15 RA48; UC57 G 1.27 0.015 0.93 0.0086 0.35 (0.007) 0.55 (3E-5) −0.31 (0.02) G ~ ORMDL3↑ (1E-10); GSDMA↓ (2E-10); GSDMB↑ (2E-9)
rs2305479† 39905964 missense GSDMB (C/T) Asthma5 C 1.34 0.0029 0.85 0.014 0.33 (0.01) 0.46 (3E-4) −0.26 (0.05) C ~ GSDMB↑ (6E-15); ORMDL3↑ (4E-15); GSDMA↓ (1E-7); PGAP3↑ (5E-6)
rs62067034† 39907485 intronic GSDMB (C/T) Asthma16 C 1.34 0.0029 0.85 0.014 0.33 (0.01) 0.46 (3E-4) −0.26 (0.05) C ~ GSDMB↑ (2E-15); ORMDL3↑ (1E-12); GSDMA↓ (1E-7); PGAP3↑ (7E-6)
rs11078927*† 39908152 intronic GSDMB C/T Asthma8,17 C 1.26 0.018 0.95 0.0073 0.37 (0.005) 0.56 (2E-5) −0.35 (0.009) C ~ ORMDL3↑ (1E-10); GSDMA↓ (3E-10); GSDMB↑ (9E-10)
rs11078928* 39908216 receptor GSDMB T/C eQTL for GSDMB18 T 1.26 0.018 0.95 0.0073 0.37 (0.005) 0.56 (2E-5) −0.35 (0.009) T ~ ORMDL3↑ (8E-11); GSDMA↓ (4E-10); GSDMB↑ (8E-10)
rs117097909† 39908718 intronic GSDMB A/G Asthma13 A 1.04 0.860 −0.04 0.95 0.27 (0.37) 0.52 (0.09) 0.21 (0.49) NA
rs2290400*† 39909987 intronic GSDMB T/C (C/T) Asthma19 T1D58 3 4 T 1.32 0.0044 0.84 0.016 0.40 (0.003) 0.41 (0.003) −0.35 (0.01) T ~ GSDMB↑ (8E-16); ORMDL3↑ (7E-15); GSDMA↓ (1E-8); PGAP3↑ (3E-6)
rs4795400† 39910767 intronic GSDMB (C/T) Allergy10 C 1.27 0.015 0.91 0.0093 0.35 (0.007) 0.55 (3E-5) −0.31 (0.02) C ~ ORMDL3↑ (2E-10); GSDMB↑ (3E-10); GSDMA↓ (5E-10)
rs869402† 39911790 intronic GSDMB (C/T) Asthma20 C 1.33 0.0039 0.81 0.019 0.31 (0.01) 0.41 (1E-3) −0.24 (0.06) C ~ GSDMB↑ (1E-15); ORMDL3↑ (2E-12); GSDMA↓ (2E-7); PGAP3↑ (3E-6)
rs921650† 39912823 intronic GSDMB A/G Allergy29 A 1.32 0.0045 0.80 0.021 0.33 (0.009) 0.47 (2E-4) −0.27 (0.03) A ~ GSDMB↑ (1E-15); ORMDL3↑ (8E-13); GSDMA↓ (2E-7); PGAP3↑ (3E-6)
rs7216389*† 39913696 intronic GSDMB T/C Asthma1 T 1.32 0.0045 0.80 0.021 0.33 (0.009) 0.47 (2E-4) −0.27 (0.03) T ~ GSDMB↑ (1E-15); ORMDL3↑ (8E-13); GSDMA↓ (2E-7); PGAP3↑ (3E-6)
rs9303280† 39917778 intronic GSDMB C/T Allergy30 C 1.32 0.0049 0.77 0.028 0.37 (0.004) 0.49 (1E-4) −0.33 (0.01) C ~ GSDMB↑ (3E-15); ORMDL3↑ (2E-12); GSDMA↓ (3E-9); PGAP3↑ (9E-6)
rs4065275* 39924612 intronic ORMDL3 G/A ORMDL3 promoter11 G 1.31 0.0064 0.82 0.020 0.31 (0.02) 0.36 (0.008) −0.29 (0.04) G ~ GSDMB↑ (1E-13); ORMDL3↑ (1E-13); GSDMA↓ (6E-11)
rs8076131* 39924659 intronic ORMDL3 A/G Early wheeze21 A 1.25 0.022 0.85 0.015 0.36 (0.007) 0.47 (3E-4) −0.37 (0.006) A ~ GSDMA↓ (1E-11); ORMDL3↑ (7E-11); GSDMB↑ (1E-9)
rs12603332* 39926554 5′ UTR ORMDL3 C/T eQTL and meQTL for O RMD L3/GSDMB22–23 4 5 C 1.31 0.0060 0.83 0.018 0.29 (0.03) 0.40 (0.003) −0.44 (9E-4) C ~ ORMDL3↑ (2E-14); GSDMB↑ (2E-13); GSDMA↓ (6E-12); PGAP3↑ (2E-5)
rs4794820† 39933091 intronic ORMDL3 (G/A) Asthma24 G 1.26 0.021 0.94 0.0077 0.28 (0.04) 0.40 (0.002) −0.38 (0.004) G ~ GSDMA↓ (2E-17); ORMDL3↑ (2E-11); GSDMB↑ (2E-8)
rs6503525† 39938921 intergenic ORMDL3-LRRC3C (C/G) Asthma25 5 C 1.23 0.038 0.57 0.12 0.25 (0.06) 0.076 (0.6) −0.37 (0.005) C ~ GSDMA↓ (6E-21); GSDMB↑ (9E-8); ORMDL3↑ (2E-5)
rs3902025† 39963001 5′ UTR GSDMA C/A SS59 6 C 0.81 0.033 −0.65 0.072 −0.30 (0.02) −0.23 (0.09) 0.48 (3E-4) C ~ GSDMA↑ (2E-21); ORMDL3↓ (9E-7); GSDMB↓ (1E-5)
rs3894194*† 39965740 missense GSDMA A/G G/A Asthma14–15 SS60 A 1.14 0.20 0.33 0.35 0.36 (0.006) 0.10 (0.4) −0.46 (4E-4) A ~ GSDMA↓ (1E-21); GSDMB↑ (4E-9); ORMDL3↑ (2E-7)
rs7212938† 39966427 missense GSDMA G/T Asthma9 G 1.14 0.19 0.28 0.44 0.27 (0.04) 0.14 (0.3) −0.28 (0.03) G ~ GSDMA↓ (3E-18); GSDMB↑ (1E-7); ORMDL3↑ (5E-5)
rs3859192* 39972395 intronic GSDMA T/C eQTL for GSDMA26 T 0.96 0.68 0.44 0.23 0.41 (0.002) 0.19 (0.2) −0.42 (0.001) T ~ GSDMA↓ (5E-52)
rs11652139† 39992780 intronic PSMD3 (A/G) Allergy29 A 1.01 0.90 0.47 0.19 0.32 (0.02) 0.29 (0.03) −0.17 (0.2) NA

Note: entries with p-value<0.0035 for genetic association analysis of asthma severity or longitudinal asthma exacerbations were labeled in red color. NS: non-significant; NA: non-available.

*

17 SNPs associated with asthma and reported by Stein et al.62

†

SNPs associated with asthma, allergy, and autoimmune diseases from NHGRI-EBI GWAS catalog (www.ebi.ac.uk/gwas/),78 incorporated in UCSC genome browser (genome.ucsc.edu; accessed on March 1, 2019).79

‡

Risk allele/Other allele: parenthesis indicates risk allele was not reported in the original study but predicted based on available data.

**

AD: autoimmune diseases; CD: Crohn’s disease; IBD: inflammatory bowel disease; MS: multiple sclerosis; PBCh: primary biliary cholangitis; PBCi: primary biliary cirrhosis; RA: rheumatoid arthritis; SLE: systemic lupus erythematosus; SS: systemic sclerosis; T1D: type I diabetes; UC: ulcerative colitis.

††

LD was estimated with 95% confidence intervals of D’ to define LD blocks of 48 SNPs for 1,016 non-Hispanic Whites (NHW) and 622 African Americans (AA) in SARP longitudinal cohort and cross-sectional cohort with WGS using Haploview.81

***

OR and P were odds ratio and p-value for genetic association analysis of asthma severity (426 severe vs. 531 non-severe asthma) in non-Hispanic White in SARP.

†††

β and P were correlation coefficient and p-value for genetic association analysis of the number of longitudinal exacerbations due to asthma in 3 years in the longitudinal cohort in 273 asthmatics with longitudinal asthma exacerbations in non-Hispanic White in SARP.