The Functional Copy Number Variation-67048 in WWOX Contributes to Increased Risk of COPD in Southern and Eastern Chinese

Figures & data

Figure 1.  (A) Genomic structure, locations of the CNVs in WWOX gene. (B) WWOX CNV-67048 genotyping.

Table 1.  Frequency distributions of selected variables in COPD cases and controls

Variables	Southern Chinese			Eastern Chinese			P^b
	Cases n (%)	Controls n (%)	P^a	Cases n (%)	Controls n (%)	P^a
Total No. of subjects	1025	1061		766	879
Age (mean, range, y)	61.2,76	60.8,48	0.303	66.0,63	64.4,54	0.106
Sex
Male	610 (59.5)	638 (60.1)	0.773	478 (62.4)	551 (62.7)	0.906	0.920
Female	415 (40.5)	423 (39.9)		288 (37.6)	328 (37.3)
Smoking status
Ever	499 (48.7)	424 (40.0)	<0.001	404 (52.7)	357 (40.6)	<0.001	0.310
Never	526 (51.3)	637 (60.0)		362 (47.3)	522 (59.4)
Pack-years smoked
≥20	314 (30.6)	214 (20.2)	<0.001	306 (39.9)	257 (29.2)	<0.001	0.292
<20	185 (18.1)	210 (19.8)		98 (12.8)	100 (11.4)
0	526 (51.3)	637 (60.0)		362 (47.3)	522 (59.4)
Biomass as fuels
Yes	174 (17.0)	91 (8.6)	<0.001	112 (14.6)	81 (9.2)	0.001	<0.001
No	851 (83.0)	970 (91.4)		654 (85.4)	112 (14.6)
Drinking status
Ever	186 (18.2)	209 (19.7)	0.389	147 (19.2)	208 (23.7)	0.028	0.303
Never	834 (81.8)	851 (80.3)		619 (80.8)	671 (76.3)
Gold stages
I	359 (35.0)			324 (42.5)
II	356 (34.7)			340 (44.6)
III	217 (21.2)			75 (9.9)
IV	93 (9.1)			23 (3.0)
Pre-FEV1 (mean ± SD, L)	1.67 ± 0.62	2.29 ± 0.63	<0.001	1.61 ± 0.63	2.19 ± 0.60	<0.001
Pre-FVC (mean ± SD, L)	2.52 ± 0.87	2.84 ± 0.83	<0.001	2.44 ± 0.90	2.72 ±0.77	<0.001
Pre-FEV1/FVC (mean ± SD, L)	0.59 ± 0.10	0.81 ± 0.06	<0.001	0.60 ± 0.09	0.82 ± 0.06	<0.001

^ap values for a two-sided χ² test or student's t test.

^bp values for the Breslow-Day test of homogeneity.

Table 2.  Frequency distribution of CNV-67048 copy numbers and their associations with COPD risk

CNV-67048 genotypes	Cases n (%)	Controls n (%)	p value^a	Crude OR (95%CI)	Adjusted OR (95%CI)^b
Southern Chinese	1025	1061
2	700 (68.6)	772 (72.8)	0.046	1.00 (ref.)	1.00 (ref.)
1	287 (28.2)	267 (25.2)		1.19 (0.98–1.44)	1.20 (0.98–1.46)
0	33 (3.2)	21 (2.0)		1.73 (0.99–3.02)	1.65 (0.93–2.92)
Trend test p value				0.017	0.021
2	700 (68.6)	772 (72.8)		1.00 (ref.)	1.00 (ref.)
1 +0	320 (31.4)	288 (27.2)		1.26 (1.01–1.48)	1.23 (1.01–1.49)
loss allele	0.173	0.146	0.017
Eastern Chinese	766	879
2	524 (68.4)	661 (75.2)	0.009	1.00 (ref.)	1.00 (ref.)
1	221 (28.9)	201 (22.9)		1.39 (1.11–1.73)	1.34 (1.07–1.69)
0	21 (2.7)	17 (1.9)		1.56 (0.81–2.98)	1.60 (0.81–3.14)
Trend test P value				0.003	0.007
2	524 (68.4)	661 (75.2)		1.00 (ref.)	1.00 (ref.)
1 +0	167 (33.2)	158 (25.4)		1.40 (1.13–1.74)	1.36 (1.09–1.70)
loss allele	0.172	0.134	0.008
Merged population	1791	1940
2	1224 (68.5)	1433 (73.9)	0.001	1.00 (ref.)	1.00 (ref.)
1	508 (28.5)	468 (24.1)		1.27 (1.10–1.47)	1.26 (1.08–1.47)
0	54 (3.0)	38 (2.0)		1.66 (1.09–2.54)	1.63 (1.05–2.51)
Trend test p value				1.00 ×10^−4	4.00 ×10^−4
2	1224 (68.5)	1433 (73.9)		1.00 (ref.)	1.00 (ref.)
1 +0	562 (31.5)	506 (26.1)		1.30 (1.13–1.50)	1.29 (1.11–1.49)
loss allele	0.173	0.140	1.30 × 10^−4

*Bold type: statistically significant, P < 0.05.

^aThe two-sided χ² test for assessing differences between copy number frequency of CNV-67048 between cases and controls.

^bAdjusted in the unconditional logistic regression model with age, sex, smoking status, biomass as fuels, drinking status and population as co-variables.

Figure 2.  Effect of the CNV-67048 on lung function: (A) On pre-FEV₁/FVC. (B) On pre-FEV₁. (C) On pre-FVC. (D) On the annual decline of pre-FEV₁.