Table 4.
Interaction between the overall GRS and respiratory tract diseases for incident RA risk, stratified by serostatus
| Adjusted* OR (95% CI) | Overall GRS-Respiratory Interactions | |||||
|---|---|---|---|---|---|---|
| Respiratory tract disease | GRS-low/Resp+ | GRS-high/Resp− | GRS-high/Resp+ | AP (95% CI) | RERI (95% CI) | Multiplicative OR |
| Seropositive RA outcomes (n=373) | ||||||
| Any respiratory tract disease | 1.40 (0.94,2.07) | 4.68 (3.21,6.84) | 3.76 (2.54,5.57) | −0.35 (−0.83,0.13) | −1.32 (−2.98,0.35) | 0.74 (0.59,0.94) |
| Asthma | 1.26 (0.71,2.22) | 3.61 (2.70,4.81) | 4.15 (2.44,7.07) | 0.07 (−0.42,0.56) | 0.29 (−1.88,2.45) | 0.91 (0.65,1.26) |
| Interstitial lung disease | 2.60 (0.43,15.59) | 3.57 (2.71,4.69) | 5.54 (1.46,21.12) | 0.07 (−1.00,1.00) | 0.38 (−8.33,9.09) | 2.33 (0.58,9.47) |
| Pharyngitis | 1.33 (0.72,2.45) | 3.61 (2.71,4.82) | 4.58 (2.51,8.36) | 0.14 (−0.38,0.66) | 0.64 (−2.05,3.33) | 0.85 (0.59,1.22) |
| Acute pharyngitis | 1.13 (0.54,2.35) | 3.51 (2.65,4.66) | 5.08 (2.59,9.95) | 0.28 (−0.20,0.77) | 1.44 (−1.87,4.76) | 0.90 (0.60,1.35) |
| Chronic rhinitis/pharyngitis | 2.00 (0.81,4.93) | 3.67 (2.78,4.84) | 4.33 (1.50,12.51) | −0.08 (−1.00,1.00) | −0.33 (−5.18,4.51) | 0.86 (0.46,1.64) |
| Pneumonia and acute lowerdiseases | 1.39 (0.77,2.53) | 3.59 (2.70,4.77) | 4.86 (2.64,8.94) | 0.18 (−0.33,0.69) | 0.88 (−2.07,3.82) | 0.95 (0.65,1.39) |
| Sinusitis | 1.66 (0.85,3.23) | 3.76 (2.83,5.01) | 3.45 (1.91,6.24) | −0.28 (−1.07,0.51) | −0.97 (−3.25,1.32) | 0.77 (0.52,1.15) |
| Acute sinusitis | 1.68 (0.72,3.94) | 3.66 (2.76,4.83) | 3.93 (1.82,8.51) | −0.10 (−1.00,0.79) | −0.41 (−3.65,2.84) | 0.73 (0.44,1.22) |
| Chronic sinusitis | 2.02 (0.90,4.55) | 3.85 (2.90,5.10) | 2.19 (1.04,4.61) | −1.23 (−3.03,0.57) | −2.58 (−5.15,−0.21) | 0.64 (0.40,1.02) |
| Seronegative RA (n=268) | ||||||
| Any respiratory tract disease | 1.02 (0.71,1.48) | 1.44 (0.95,2.19) | 1.27 (0.83,1.94) | −0.15 (0.75,0.45) | −0.19 (−0.94,0.55) | 0.84 (0.64,1.10) |
| Asthma | 1.10 (0.67,1.81) | 1.47 (1.07,2.00) | 0.80 (0.39,1.66) | −0.96 (−1.00,0.62) | −0.77 (−1.66,0.12) | 0.80 (0.55,1.16) |
| Interstitial lung disease | 0.95 (0.18,4.92) | 1.34 (1.00,1.79) | N/A | N/A | −1.29 (−2.92,0.35) | 0.33 (0.06,1.99) |
| Pharyngitis | 1.98 (1.17,3.34) | 1.42 (1.04,1.92) | 1.69 (0.82,3.49) | −0.41 (−1.00,0.73) | −0.70 (−2.26,0.86) | 0.84 (0.56,1.26) |
| Acute pharyngitis | 2.33 (1.29,4.21) | 1.38 (1.02,1.87) | 2.35 (1.05,5.24) | −0.15 (−1.00,0.90) | −0.36 (−2.61,1.89) | 0.82 (0.53,1.28) |
| Chronic rhinitis/pharyngitis | 1.10 (0.45,2.68) | 1.39 (1.04,1.86) | 0.30 (0.04,2.33) | N/A | −1.19 (−2.41,0.03) | 0.52 (0.21,1.32) |
| Pneumonia and acute lowerdiseases | 1.29 (0.69,2.40) | 1.33 (0.81,1.80) | 1.64 (0.81,3.32) | 0.01 (−0.83,0.86) | 0.02 (−1.38,1.41) | 0.83 (0.54,1.26) |
| Sinusitis | 1.44 (0.79,2.64) | 1.36 (1.01,1.85) | 1.53 (0.74,3.16) | −0.19 (−1.00,0.83) | −0.28 (−1.69,1.12) | 0.73 (0.47,1.14) |
| Acute sinusitis | 2.23 (1.03,4.80) | 1.39 (1.03,1.86) | 1.55 (0.50,4.75) | −0.69 (−1.00,1.00) | −1.06 (−3.47,1.34) | 0.67 (0.36,1.25) |
| Chronic sinusitis | 0.95 (0.44,2.08) | 1.30 (0.97,1.76) | 1.67 (0.75,3.73) | 0.25 (−0.51,1.00) | 0.41 (−1.10,1.93) | 0.90 (0.53,1.50) |
AP = attributable proportion, CI = confidence interval, COPD = chronic obstructive pulmonary disease, GRS = genetic risk score, HLA = human leukocyte antigen, N/A = not applicable due to small sample size, OR = odds ratio, RA = rheumatoid arthritis, RERI = relative excess risk due to interaction, Resp = respiratory tract exposure
*
Reference group was individuals without respiratory tract disease exposure and lowest two GRS tertiles. Adjusting for age, sex, EHR history, enrollment year, race and ethnicity by principal components, education, body mass index, smoking status, and pack-years. Bold values are statistically significant.