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. 2020 Sep 15;202(6):853–865. doi: 10.1164/rccm.201912-2338OC

Table 4.

Results from External Replication in CHARGE and SpiroMeta for the 17 Signals for FVC

Gene SNP Chr EA EAF Internal Replication
 External Replication
UKB Stage 2 (N = 138,411)
 CHARGE
 SpiroMeta
 Meta-Analysis CHARGE + SpiroMeta
β SE P Value N β SE P Value n Direction P Value P Value
ACTN3 rs57127845 11 C 0.82 −14.7 2.9 2.3 × 10−7 60,507 −11.2 4.2 3.6 × 10−3 75,423 + 0.473† 0.014
ACTN4 rs189809900 19 A 0.98 −35.8 8.9 2.8 × 10−5 36,112 4.7 21.3 0.414† 81,081 — 0.232 0.407
CLDN20 rs34268254 6 TA 0.39 9.0 2.3 4.6 × 10−5 60,507‡ 7.9‡ 3.2‡ 6.4 × 10−3 ‡ 75,422‡ +‡ 0.011‡ 7.4 × 10−4 *
GSK3B rs6805251 3 T 0.38 8.0 2.3 2.1 × 10−4 60,506 4.9 3.2 0.064 74,551 + 0.083 0.033
HOXA1 rs45571645 7 G 0.98 28.7 8.3 2.9 × 10−4 58,929 2.3 12.0 0.425 82,863 — 0.481† 0.559
HOXB4 rs201603635 17 T 0.94 −16.3 4.6 1.9 × 10−4 NA NA NA NA NA NA NA NA
ITGB5 rs17282078 3 T 0.87 15.7 3.3 9.0 × 10−7 60,508 13.5 4.7 2.0 × 10−3 * 75,422 + 0.365 6.1 × 10−3
KAT8 rs138259061 16 A 0.64 −7.7 2.3 4.5 × 10−4 60,508§ −6.2 § 3.3§ 0.029 § 82,865 — 0.099 0.020
MMP24 rs7280 20 A 0.58 9.7 2.3 9.5 × 10−6 60,508 8.5 3.3 5.1 × 10−3 81,992 + 0.014 7.5 × 10−4 *
NCOR2 rs72451021 12 ACT 0.89 12.8 3.6 1.9 × 10−4 45,256 1.9 5.9 0.372 75,422‖ +‖ 0.038 ‖ 0.074
NR3C1 rs72801051 5 A 0.84 10.7 3.0 1.6 × 10−4 60,507 7.5 4.4 0.046 75,421 + 0.111 0.032
ROR2 rs12684752 9 T 0.94 −17.8 4.7 8.5 × 10−5 60,506 −2.5 6.6 0.353 75,421 — 0.398 0.415
RUNX1 rs12483501 21 T 0.63 10.1 2.5 2.1 × 10−5 60,508 4.0 3.9 0.150 81,992 + 0.026 0.026
SERPINC1 rs2227603 1 A 0.97 −23.1 6.6 2.5 × 10−4 60,508 −20.6 10.0 0.020 75,423 — 0.367 0.044
SOX9 rs796209434 17 CT 0.53 7.9 2.2 2.0 × 10−4 60,506 10.4 3.2 5.4 × 10−4 * 75,422 + 8.3 × 10−3 6.0 × 10−5 *
WNT2B rs351370 1 C 0.41 7.7 2.2 3.2 × 10−4 60,506 7.4 3.4 0.014 74,550 + 3.2 × 10−3 4.9 × 10−4 *
WNT9A rs35799012 1 C 0.83 −13.5 2.9 2.2 × 10−6 60,508 −9.4 4.7 0.024 74,552 — 2.8 × 10−3 * 7.1 × 10−4 *

Definition of abbreviations: CHARGE = Cohorts for Heart and Aging Research in Genomic Epidemiology; Chr = chromosome; EA = effect allele; EAF = EA frequency; NA = not available; UKB = UK Biobank.

Analyses in the whole dataset (N = 346,027). For SpiroMeta, reported only effect direction because β not interpretable (use of rank-based inverse normal transformation). In bold are external replication results with P < 0.05. β values are per-allele effect estimates.

*

External replication results significant at Bonferroni (P < 3.1 × 10−3).

†

P value inverted in Fisher’s meta-analysis to reflect the effect in opposite direction (P values reported for UKB stage 2, CHARGE, and SpiroMeta are all one-sided, see text).

‡

Proxy: rs13220615 (r2 = 0.97).

§

Proxy: rs1978485 (r2 = 0.98).

‖

Proxy: rs11057583 (r2 = 1.0).

Proxy: rs1042678 (r2 = 0.97).